Trial Outcomes & Findings for Sorafenib Combined With Erlotinib, Tipifarnib, or Temsirolimus in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma (NCT NCT00335764)
NCT ID: NCT00335764
Last Updated: 2018-07-02
Results Overview
DLT defined as: any grade 4 hematologic toxicity; grade 3 thrombocytopenia \> 7 days, any grade 3/4 non-hematologic toxicity (despite maximal medical therapy), any intolerable grade 2 non-hematological, ro grade 3 hematological toxicity requiring deduction during first 28 days of treatment, any toxicity resulting in delay of \>1week during first 28 days of treatment
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
92 participants
Primary outcome timeframe
28 days
Results posted on
2018-07-02
Participant Flow
patients enrolled from 2006 - 2009 Patients accrued from comprehensive outpatient cancer centers
Participant milestones
| Measure |
Group 1 Phase I Sorafenib and Erlotinib
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)
erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD
|
Group 2 Phase I Sorafenib and Temsirolimus
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW
|
Group 3 Phase I Sorafenib and Tipifarnib
Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID
|
Group 1 Phase II Sorafenib and Erlotinib
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally
erlotinib hydrochloride: given orally
|
Group 2 Phase II Sorafenib and Temsirolimus
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV 25 mg over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally 400mg BID
temsirolimus: IV administration 25mg IV QW
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
17
|
13
|
24
|
19
|
19
|
|
Overall Study
COMPLETED
|
16
|
13
|
24
|
19
|
18
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Group 1 Phase I Sorafenib and Erlotinib
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)
erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD
|
Group 2 Phase I Sorafenib and Temsirolimus
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW
|
Group 3 Phase I Sorafenib and Tipifarnib
Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID
|
Group 1 Phase II Sorafenib and Erlotinib
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally
erlotinib hydrochloride: given orally
|
Group 2 Phase II Sorafenib and Temsirolimus
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV 25 mg over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally 400mg BID
temsirolimus: IV administration 25mg IV QW
|
|---|---|---|---|---|---|
|
Overall Study
wrong histology
|
1
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Sorafenib Combined With Erlotinib, Tipifarnib, or Temsirolimus in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma
Baseline characteristics by cohort
| Measure |
Group 1 Phase I Sorafenib and Erlotinib
n=16 Participants
Patients receive oral sorafenib tosylate twice daily and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally
erlotinib hydrochloride: given orally
|
Group 2 Phase I Sorafenib and Temsirolimus
n=13 Participants
Patients receive sorafenib tosylate as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally
temsirolimus: IV administration
|
Group 3 Phase I Sorafenib and Tipifarnib
n=24 Participants
Patients receive sorafenib tosylate as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally
tipifarnib: given orally
|
Group 1 Phase II Sorafenib and Erlotinib
n=19 Participants
Patients receive oral sorafenib tosylate twice daily and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally
erlotinib hydrochloride: given orally
|
Group 2 Phase II Sorafenib and Temsirolimus
n=18 Participants
Patients receive sorafenib tosylate 400 mg BID as in group 2. Patients also receive temsirolimus IV 25 mg over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally
temsirolimus: IV administration
|
Total
n=90 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
53 years
n=99 Participants
|
50 years
n=107 Participants
|
57 years
n=206 Participants
|
52 years
n=7 Participants
|
50 years
n=31 Participants
|
53 years
n=30 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
10 Participants
n=7 Participants
|
9 Participants
n=31 Participants
|
38 Participants
n=30 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
9 Participants
n=7 Participants
|
9 Participants
n=31 Participants
|
52 Participants
n=30 Participants
|
|
Karnofsky Performance Status Scale
|
90 units on a scale
n=99 Participants
|
80 units on a scale
n=107 Participants
|
85 units on a scale
n=206 Participants
|
90 units on a scale
n=7 Participants
|
90 units on a scale
n=31 Participants
|
90 units on a scale
n=30 Participants
|
PRIMARY outcome
Timeframe: 28 daysPopulation: 3+3 design due to excessive toxicities of Group 3 no DLT was defined for Group 3
DLT defined as: any grade 4 hematologic toxicity; grade 3 thrombocytopenia \> 7 days, any grade 3/4 non-hematologic toxicity (despite maximal medical therapy), any intolerable grade 2 non-hematological, ro grade 3 hematological toxicity requiring deduction during first 28 days of treatment, any toxicity resulting in delay of \>1week during first 28 days of treatment
Outcome measures
| Measure |
Group 1 Phase I Sorafenib and Erlotinib QD
n=16 Participants
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)
erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD
|
Group 2 Phase I Sorafenib and Temsirolimus QW
n=13 Participants
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW
|
Group 3 Phase I Sorafenib and Tipifarnib BID
n=24 Participants
Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID
|
|---|---|---|---|
|
Maximum Tolerated Dose (MTD) of the Each Combination Agent Combined With a Fixed Dose of BAY 43-9006 Determined by Dose-limiting Toxicities (DLT) (Phase I)
|
100 mg
|
25 mg
|
NA mg
due to the excessive toxicities of Group 3 no DLT was defined
|
PRIMARY outcome
Timeframe: cycle 1 ((Day1, Day15, Day28)Population: Group 2: total 13 patients were studied for their day 1 Cmax ,day 15 Cmax and day 28 Cmax Note that although 13 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference
Group 2: 13 patients received temsirolimus 25mg IV and 7 patients treated with 200mg Sorafenib and 6 patients treated with 400mg Sorafenib
Outcome measures
| Measure |
Group 1 Phase I Sorafenib and Erlotinib QD
n=13 Participants
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)
erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD
|
Group 2 Phase I Sorafenib and Temsirolimus QW
n=7 Participants
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW
|
Group 3 Phase I Sorafenib and Tipifarnib BID
n=6 Participants
Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID
|
|---|---|---|---|
|
Pharmacokinetic Max Concentration (Cmax) of Group 2 Sorafenib and Temsirolimus (Phase I)
Day 1 Cmax
|
530 ng/mL
Standard Deviation 101
|
NA ng/mL
Standard Deviation NA
specimens not collected on day 1
|
NA ng/mL
Standard Deviation NA
specimens not collected on day 1
|
|
Pharmacokinetic Max Concentration (Cmax) of Group 2 Sorafenib and Temsirolimus (Phase I)
Day 15 Cmax
|
616 ng/mL
Standard Deviation 209
|
4.04 ng/mL
Standard Deviation 1.68
|
7.49 ng/mL
Standard Deviation 3.46
|
|
Pharmacokinetic Max Concentration (Cmax) of Group 2 Sorafenib and Temsirolimus (Phase I)
Day 28 Cmax
|
NA ng/mL
Standard Deviation NA
specimens not collected on day 28
|
3.26 ng/mL
Standard Deviation 1.34
|
6.24 ng/mL
Standard Deviation 4.03
|
PRIMARY outcome
Timeframe: 28days (D1, D15, D28) (0,1,2,4,6,8,12,24hr post administration)Population: 8 samples collected over 24 hours on Day 1, day 15 and day 28 (0,1,2,4,6,8,12hr, \& 24hr post administration). Note that although 16 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference
8 samples collected over 24 hours on Day 1, day 15 and day 28 13 total patients treated 100mg Erlotinib and either 200mg or 400mg of Sorafenib
Outcome measures
| Measure |
Group 1 Phase I Sorafenib and Erlotinib QD
n=16 Participants
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)
erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD
|
Group 2 Phase I Sorafenib and Temsirolimus QW
n=9 Participants
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW
|
Group 3 Phase I Sorafenib and Tipifarnib BID
n=6 Participants
Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID
|
|---|---|---|---|
|
Pharmacokinetic cMax Group 1 Sorafenib and Erlotinib (Phase I)
cMax Day 1
|
443 ng/mL
Standard Deviation 155
|
NA ng/mL
Standard Deviation NA
Specimens not collected/drug not given on Day 1
|
NA ng/mL
Standard Deviation NA
Specimens not collected/drug not given on Day 1
|
|
Pharmacokinetic cMax Group 1 Sorafenib and Erlotinib (Phase I)
cMax Day 15
|
662 ng/mL
Standard Deviation 373
|
5.51 ng/mL
Standard Deviation 2.68
|
8.4 ng/mL
Standard Deviation 5.18
|
|
Pharmacokinetic cMax Group 1 Sorafenib and Erlotinib (Phase I)
cMax Day 28
|
653 ng/mL
Standard Deviation 469
|
4.67 ng/mL
Standard Deviation 2.10
|
4.10 ng/mL
Standard Deviation 0.56
|
PRIMARY outcome
Timeframe: 28Days (D1, D15, D28) (0,1,2,4,6,8,12,24hr post administration) AUC 0-12Population: 8 samples collected over 24 hours on Day 1, day 15 and day 28 AUC 0-12 16 patients treated at 100mg erlotinib,and Sorafenib at either 200 or 400mg Note that although 16 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference
8 samples collected over 24 hours on Day 1, day 15 and day 28 16 patients Note that although 16 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference AUC - Area Under Curve
Outcome measures
| Measure |
Group 1 Phase I Sorafenib and Erlotinib QD
n=16 Participants
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)
erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD
|
Group 2 Phase I Sorafenib and Temsirolimus QW
n=9 Participants
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW
|
Group 3 Phase I Sorafenib and Tipifarnib BID
n=6 Participants
Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID
|
|---|---|---|---|
|
Pharmacokinetic AUC 0-12 Group 1 Sorafenib and Erlotinib (Phase I)
AUC0-12 Day1
|
6.3 ug xhr/mL
Standard Deviation 2.61
|
NA ug xhr/mL
Standard Deviation NA
Specimens not collected/drug not given on Day 1
|
NA ug xhr/mL
Standard Deviation NA
Specimens not collected/drug not given on Day 1
|
|
Pharmacokinetic AUC 0-12 Group 1 Sorafenib and Erlotinib (Phase I)
AUC0-12 Day 15
|
6.9 ug xhr/mL
Standard Deviation 4.59
|
45.85 ug xhr/mL
Standard Deviation 21.5
|
62.4 ug xhr/mL
Standard Deviation 38
|
|
Pharmacokinetic AUC 0-12 Group 1 Sorafenib and Erlotinib (Phase I)
AUC0-12 Day 28
|
7.7 ug xhr/mL
Standard Deviation 4.05
|
40.29 ug xhr/mL
Standard Deviation 18.6
|
38.7 ug xhr/mL
Standard Deviation 9.61
|
PRIMARY outcome
Timeframe: 15 daysPopulation: Group 2: 12 patients were analyzed for Day 1, 5 patients were analyzed for Day 15. In both cases samples were either missing or not enough to analyze.
Group 2: 12 patients were analyzed for Day 1 (1 patient not evaluable), 5 patients were analyzed for Day 15 (8 patients not evaluable)
Outcome measures
| Measure |
Group 1 Phase I Sorafenib and Erlotinib QD
n=13 Participants
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)
erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD
|
Group 2 Phase I Sorafenib and Temsirolimus QW
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW
|
Group 3 Phase I Sorafenib and Tipifarnib BID
Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID
|
|---|---|---|---|
|
Trough Concentration Group 2 Sorafenib and Temsirolimus (Phase I)
Trough Day 1
|
24 ng/mL
Standard Deviation 6.92
|
—
|
—
|
|
Trough Concentration Group 2 Sorafenib and Temsirolimus (Phase I)
Trough Day 15
|
20 ng/mL
Standard Deviation 7.05
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1 (D1, D15, D28) (0,1,2,4,6,8,12,24hr post drug administration)Population: 13 patients temsirolimus 25mg and Sorafenib at either 200mg or 400mg. 1 patient withdrew early hence specimens not analyzed in other cases samples were either missing or not enough to analyze if numbers are not 12
Day 1 = 12 patients (1 sample not evaluable) Day 15 = 5 patients (8 samples not evaluable) AUC - Area Under Curve 8 samples collected over 24 hours - 28 day PKs
Outcome measures
| Measure |
Group 1 Phase I Sorafenib and Erlotinib QD
n=13 Participants
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)
erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD
|
Group 2 Phase I Sorafenib and Temsirolimus QW
n=13 Participants
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW
|
Group 3 Phase I Sorafenib and Tipifarnib BID
n=13 Participants
Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID
|
|---|---|---|---|
|
Plasma Time Curve (AUC) of Group 2 Sorafenib and Temsirolimus (Phase I)
AUC 0-12 Day 1
|
1.53 mcg*hr/mL
Standard Deviation 0.27
|
NA mcg*hr/mL
Standard Deviation NA
Samples not collected on this day, drug not given on day 1
|
NA mcg*hr/mL
Standard Deviation NA
Samples not collected on this day, drug not given on day 1
|
|
Plasma Time Curve (AUC) of Group 2 Sorafenib and Temsirolimus (Phase I)
AUC 0-12 Day 15
|
1.35 mcg*hr/mL
Standard Deviation 0.28
|
35.45 mcg*hr/mL
Standard Deviation 18.10
|
42.32 mcg*hr/mL
|
|
Plasma Time Curve (AUC) of Group 2 Sorafenib and Temsirolimus (Phase I)
AUC 0-12 Day 28
|
NA mcg*hr/mL
Standard Deviation NA
Samples not collected on this day, drug not given on day 28
|
29.0 mcg*hr/mL
Standard Deviation 12.32
|
32.98 mcg*hr/mL
Standard Deviation 0.318
|
PRIMARY outcome
Timeframe: Cycle 1 = 28 day PKs D1, D15,D28 (0,1,2,4,6,8,12,24hr post drug administration)Population: Group 3: Only PKs for Dose level 1 and -1 were collected. Note that although 6 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference
Group 3: Only PKs for Dose level 1 and -1 were collected.
Outcome measures
| Measure |
Group 1 Phase I Sorafenib and Erlotinib QD
n=6 Participants
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)
erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD
|
Group 2 Phase I Sorafenib and Temsirolimus QW
n=6 Participants
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW
|
Group 3 Phase I Sorafenib and Tipifarnib BID
Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID
|
|---|---|---|---|
|
Pharmacokinetic Cpmax Group 3 Sorafenib and Tipifarnib (Phase I) 100 mg QD (Level -1)
Cmax Day 28
|
NA ng/mL
Standard Deviation NA
Samples not collected on day 28, drug not given on day 28
|
3.43 ng/mL
Standard Deviation 1.46
|
—
|
|
Pharmacokinetic Cpmax Group 3 Sorafenib and Tipifarnib (Phase I) 100 mg QD (Level -1)
Cmax Day 1
|
209.5 ng/mL
Standard Deviation 135.85
|
NA ng/mL
Standard Deviation NA
Samples not collected on day 1, drug not given on day 1
|
—
|
|
Pharmacokinetic Cpmax Group 3 Sorafenib and Tipifarnib (Phase I) 100 mg QD (Level -1)
Cmax Day 15
|
169.5 ng/mL
Standard Deviation 186
|
3.34 ng/mL
Standard Deviation 1.31
|
—
|
PRIMARY outcome
Timeframe: Cycle 1 = 28 day PKs D1, D15,D28 (0,1,2,4,6,8,12,24hr post drug administration)Population: Group 3: patients were studied for their day 1 Cmax, day 15 Cmax. and Day 28 Cmax PKs for 100mg BID Tipifarnib Note that although 10 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference Level 1 (n=10): Day 1 n=6 (4 samples not evaluable) and D15 n=5 (5 samples not evaluable)
Group 3: patients were studied for their day 1 Cmax, and day 15 Cmax Tipifanib and Day 15 and Day 28 sorafenib Group 3: Only PKs for Dose level 1 and -1 were collected.
Outcome measures
| Measure |
Group 1 Phase I Sorafenib and Erlotinib QD
n=10 Participants
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)
erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD
|
Group 2 Phase I Sorafenib and Temsirolimus QW
n=10 Participants
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW
|
Group 3 Phase I Sorafenib and Tipifarnib BID
Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID
|
|---|---|---|---|
|
Pharmacokinetic CpMax Concentration of Group 3 Sorafenib and Tipifarnib (Phase I) 100mg BID
Day 1 Cmax
|
132.17 ng/mL
Standard Deviation 65.96
|
NA ng/mL
Standard Deviation NA
Samples not collected on this day, drug not given
|
—
|
|
Pharmacokinetic CpMax Concentration of Group 3 Sorafenib and Tipifarnib (Phase I) 100mg BID
Day 15 Cmax
|
233.60 ng/mL
Standard Deviation 84.83
|
4.17 ng/mL
Standard Deviation 2.99
|
—
|
|
Pharmacokinetic CpMax Concentration of Group 3 Sorafenib and Tipifarnib (Phase I) 100mg BID
Day 28 Cmax
|
NA ng/mL
Standard Deviation NA
Samples not collected on this day, drug not given
|
4.53 ng/mL
Standard Deviation 2.38
|
—
|
PRIMARY outcome
Timeframe: Cycle 1 (D1, D15, D28) (0,1,2,4,6,8,12,24hr post drug administration)Population: Group 3: PKs for Dose level -1 Tipifarnib 100mg QD Sorafenib started day 2
Group 3: PKs for Dose level -1 100mg QD Note that although 9 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference
Outcome measures
| Measure |
Group 1 Phase I Sorafenib and Erlotinib QD
n=9 Participants
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)
erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD
|
Group 2 Phase I Sorafenib and Temsirolimus QW
n=9 Participants
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW
|
Group 3 Phase I Sorafenib and Tipifarnib BID
Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID
|
|---|---|---|---|
|
Plasma Time Curve (AUC) of Group 3 Phase I Sorafenib and Tipifarnib 100mg QD (Level -1)
AUC 0-12 Day 1
|
814.5 ng*hr/mL
Standard Deviation 347.57
|
NA ng*hr/mL
Standard Deviation NA
Samples not collected on this day, drug not given
|
—
|
|
Plasma Time Curve (AUC) of Group 3 Phase I Sorafenib and Tipifarnib 100mg QD (Level -1)
AUC 0-12 Day 15
|
706 ng*hr/mL
Standard Deviation 644.88
|
30.59 ng*hr/mL
Standard Deviation 14.59
|
—
|
|
Plasma Time Curve (AUC) of Group 3 Phase I Sorafenib and Tipifarnib 100mg QD (Level -1)
AUC 0-12 Day 28
|
NA ng*hr/mL
Standard Deviation NA
Samples not collected on this day, drug not given
|
41.43 ng*hr/mL
Standard Deviation 28.82
|
—
|
PRIMARY outcome
Timeframe: Cycle 1 = 28 day PKs D1, D15,D28 (0,1,2,4,6,8,12,24hr post drug administration)Population: Group 3: PKs for Dose level 1 Tipifarnib 100mg BID
Group 3: PKs for Dose level 1 Tipifarnib 100mg BID
Outcome measures
| Measure |
Group 1 Phase I Sorafenib and Erlotinib QD
n=10 Participants
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)
erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD
|
Group 2 Phase I Sorafenib and Temsirolimus QW
n=10 Participants
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW
|
Group 3 Phase I Sorafenib and Tipifarnib BID
Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID
|
|---|---|---|---|
|
Plasma Time Curve (AUC) of Group 3 Phase I Sorafenib and Tipifarnib 100mg BID (Level 1)
AUC 0-12 Day 1
|
631.67 ng*hr/mL
Standard Deviation 431.12
|
NA ng*hr/mL
Standard Deviation NA
Samples not collected, drug not given on this day
|
—
|
|
Plasma Time Curve (AUC) of Group 3 Phase I Sorafenib and Tipifarnib 100mg BID (Level 1)
AUC 0-12 Day 15
|
390.25 ng*hr/mL
Standard Deviation 758.07
|
12.17 ng*hr/mL
Standard Deviation 16.33
|
—
|
|
Plasma Time Curve (AUC) of Group 3 Phase I Sorafenib and Tipifarnib 100mg BID (Level 1)
AUC 0-12 Day 28
|
NA ng*hr/mL
Standard Deviation NA
Samples not collected, drug not given on this day
|
36.45 ng*hr/mL
Standard Deviation 17.21
|
—
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: Group 3 did not reach an MTD Hence, did not complete the Phase 2 portion of study, combination treatment too toxic.
number of patients alive at 12 months
Outcome measures
| Measure |
Group 1 Phase I Sorafenib and Erlotinib QD
n=19 Participants
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)
erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD
|
Group 2 Phase I Sorafenib and Temsirolimus QW
n=18 Participants
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW
|
Group 3 Phase I Sorafenib and Tipifarnib BID
Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID
|
|---|---|---|---|
|
12 Month Survival Rate (Phase II)
Patients Alive at 12 Months
|
8 Participants
|
10 Participants
|
—
|
|
12 Month Survival Rate (Phase II)
Patients Dead at 12 Months
|
11 Participants
|
8 Participants
|
—
|
PRIMARY outcome
Timeframe: 28 daysCTCAE 3.0
Outcome measures
| Measure |
Group 1 Phase I Sorafenib and Erlotinib QD
n=16 Participants
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)
erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD
|
Group 2 Phase I Sorafenib and Temsirolimus QW
n=13 Participants
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW
|
Group 3 Phase I Sorafenib and Tipifarnib BID
n=24 Participants
Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID
|
|---|---|---|---|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Leukopenia Grade 3
|
0 Events
|
0 Events
|
0 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Lymphopenia Grade 3
|
0 Events
|
2 Events
|
3 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Neutropenia Grade 3
|
0 Events
|
0 Events
|
0 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Thrombocytopenia Grade 3
|
0 Events
|
1 Events
|
0 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
AST, SGOT Grade 3
|
1 Events
|
1 Events
|
0 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Cholesterol Grade 3
|
0 Events
|
1 Events
|
0 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Diarrhea Grade 3
|
0 Events
|
1 Events
|
2 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Hemmorrhoids Grade 3
|
0 Events
|
1 Events
|
0 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Hypertriglyceridemia Grade 3
|
0 Events
|
1 Events
|
0 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Hypophosphatemia Grade 3
|
3 Events
|
2 Events
|
4 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Fatigue Grade 3
|
0 Events
|
0 Events
|
1 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Vomiting Grade 3
|
0 Events
|
0 Events
|
1 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Lipase Grade 4
|
0 Events
|
0 Events
|
3 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Joint - Knee Pain Grade 3
|
0 Events
|
0 Events
|
1 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Thrombosis/thrombus/embolism Grade 4
|
0 Events
|
0 Events
|
1 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Fever Grade 3
|
0 Events
|
0 Events
|
1 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Dysphasia Grade 3
|
0 Events
|
0 Events
|
1 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Pain - Head/Headache Grade 3
|
0 Events
|
0 Events
|
1 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Encephalopathy Grade 3
|
0 Events
|
0 Events
|
1 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Lipase Grade 3
|
1 Events
|
0 Events
|
0 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
ALT, SGPT Grade 3
|
2 Events
|
0 Events
|
0 Events
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Hypertension Grade 3
|
1 Events
|
0 Events
|
0 Events
|
PRIMARY outcome
Timeframe: 1 yearOutcome measures
| Measure |
Group 1 Phase I Sorafenib and Erlotinib QD
n=19 Participants
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)
erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD
|
Group 2 Phase I Sorafenib and Temsirolimus QW
n=18 Participants
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW
|
Group 3 Phase I Sorafenib and Tipifarnib BID
Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID
|
|---|---|---|---|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Lymphopenia Grade 3
|
2 events
|
2 events
|
—
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Thrombocytopenia Grade 3
|
0 events
|
5 events
|
—
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Thrombocytopenia Grade 4
|
0 events
|
2 events
|
—
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Cholesterol (high) Grade 3
|
0 events
|
2 events
|
—
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Diarrhea Grade 3
|
1 events
|
1 events
|
—
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Fatigue Grade 3
|
3 events
|
2 events
|
—
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Hypokalemia Grade 3
|
0 events
|
1 events
|
—
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Hyponatremia Grade 3
|
0 events
|
1 events
|
—
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Hypophosphatemia Grade 3
|
0 events
|
3 events
|
—
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Lipase (high) Grade 3
|
0 events
|
1 events
|
—
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Pharyngeal mucositis Grade 3
|
0 events
|
1 events
|
—
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Pruritis Grade 3
|
0 events
|
1 events
|
—
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Rash Grade 3
|
0 events
|
1 events
|
—
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Seizures Grade 3
|
0 events
|
1 events
|
—
|
|
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Hypertension Grade 3
|
1 events
|
0 events
|
—
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: Group 3 did not reach an MTD not complete the Phase 2 portion of study, combination treatment too toxic. End points not followed for group 3 Phase 2
Patients with a scan at 6 months without progressive disease Progressive disease defined as Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion.
Outcome measures
| Measure |
Group 1 Phase I Sorafenib and Erlotinib QD
n=19 Participants
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)
erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD
|
Group 2 Phase I Sorafenib and Temsirolimus QW
n=18 Participants
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW
|
Group 3 Phase I Sorafenib and Tipifarnib BID
n=24 Participants
Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID
|
|---|---|---|---|
|
Progression-free Survival at 6 Months (Phase II)
|
15.8 weeks
Interval 3.4 to 39.6
|
8 weeks
Interval 5.0 to 9.0
|
4.2 weeks
Interval 0.1 to 21.1
|
PRIMARY outcome
Timeframe: Up to 5 yearsMeasurable: Bidimensionally measurable lesions w/ clearly defined margins by MRI Evaluable: Unidimensionally measurable lesions, masses w/margins not clearly defined. Complete Response (CR): Complete disappearance of all measurable/evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients on minimal/no steroids. Partial Response (PR): \>/= to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. Responders must be on same/decreasing doses of dexamethasone. Stable/No Response: Does not qualify for CR, PR, or progression. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over BL if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Outcome measures
| Measure |
Group 1 Phase I Sorafenib and Erlotinib QD
n=19 Participants
Patients receive oral sorafenib tosylate BID and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)
erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD
|
Group 2 Phase I Sorafenib and Temsirolimus QW
n=18 Participants
Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW
|
Group 3 Phase I Sorafenib and Tipifarnib BID
Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID
tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID
|
|---|---|---|---|
|
Objective Response Rate in Patients With Measurable Disease (Phase II)
Partial Response
|
0 Participants
|
2 Participants
|
—
|
|
Objective Response Rate in Patients With Measurable Disease (Phase II)
Complete Response
|
0 Participants
|
0 Participants
|
—
|
|
Objective Response Rate in Patients With Measurable Disease (Phase II)
Stable Response
|
7 Participants
|
3 Participants
|
—
|
|
Objective Response Rate in Patients With Measurable Disease (Phase II)
Progressive Disease
|
10 Participants
|
13 Participants
|
—
|
|
Objective Response Rate in Patients With Measurable Disease (Phase II)
Unevaluable
|
2 Participants
|
0 Participants
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 28 daysPopulation: this was more an exploratory correlative and as per the pre-specified protocol, was only to be performed if the outcome of other parts of the study indicated positive results.
Examination of tissue markers of signal transduction pathways by immunohistochemical analysis this was an exploratory measure and it was not explore due to the negative results of the rest of the study
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 28 daysPopulation: This was more an exploratory correlative and as per the pre-specified protocol, was only to be performed if the outcome of other parts of the study indicated positive results.
Determine the relationship between tumor and blood biomarkers and clinical outcome of patients this was more an exploratory correlative and was not completed due to the negative outcome of other parts of the study
Outcome measures
Outcome data not reported
Adverse Events
Group 1 Phase I Sorafenib and Erlotinib
Serious events: 0 serious events
Other events: 13 other events
Deaths: 15 deaths
Group 2 Phase I Sorafenib and Temsirolimus
Serious events: 0 serious events
Other events: 8 other events
Deaths: 13 deaths
Group 3 Phase I Sorafenib and Tipifarnib
Serious events: 4 serious events
Other events: 15 other events
Deaths: 24 deaths
Group 1 Phase II Sorafenib and Erlotinib
Serious events: 1 serious events
Other events: 11 other events
Deaths: 19 deaths
Group 2 Phase II Sorafenib and Temsirolimus
Serious events: 2 serious events
Other events: 12 other events
Deaths: 18 deaths
Serious adverse events
| Measure |
Group 1 Phase I Sorafenib and Erlotinib
n=16 participants at risk
Patients receive oral sorafenib tosylate twice daily and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally
erlotinib hydrochloride: given orally
|
Group 2 Phase I Sorafenib and Temsirolimus
n=13 participants at risk
Patients receive sorafenib tosylate as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally
temsirolimus: IV administration
|
Group 3 Phase I Sorafenib and Tipifarnib
n=24 participants at risk
Patients receive sorafenib tosylate as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally
tipifarnib: given orally
|
Group 1 Phase II Sorafenib and Erlotinib
n=19 participants at risk
Patients receive oral sorafenib tosylate twice daily and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally
erlotinib hydrochloride: given orally
|
Group 2 Phase II Sorafenib and Temsirolimus
n=18 participants at risk
Patients receive sorafenib tosylate 400 mg BID as in group 2. Patients also receive temsirolimus IV 25 mg over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally
temsirolimus: IV administration
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
4.2%
1/24 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Psychiatric disorders
Confusion
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
4.2%
1/24 • Number of events 1 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
5.6%
1/18 • Number of events 1 • 2 years
CTCAE
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
4.2%
1/24 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Vascular disorders
Hypertension
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
4.2%
1/24 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Investigations
Lipase increased
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
4.2%
1/24 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Nervous system disorders
Headache
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
4.2%
1/24 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Infections and infestations
Pancrease infection
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
4.2%
1/24 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
4.2%
1/24 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Nervous system disorders
Seizure
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
5.6%
1/18 • Number of events 1 • 2 years
CTCAE
|
|
Investigations
Serum amylase increased
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
4.2%
1/24 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Vascular disorders
Thromboembolic event
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
4.2%
1/24 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
5.6%
1/18 • Number of events 1 • 2 years
CTCAE
|
Other adverse events
| Measure |
Group 1 Phase I Sorafenib and Erlotinib
n=16 participants at risk
Patients receive oral sorafenib tosylate twice daily and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally
erlotinib hydrochloride: given orally
|
Group 2 Phase I Sorafenib and Temsirolimus
n=13 participants at risk
Patients receive sorafenib tosylate as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally
temsirolimus: IV administration
|
Group 3 Phase I Sorafenib and Tipifarnib
n=24 participants at risk
Patients receive sorafenib tosylate as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.
sorafenib tosylate: given orally
tipifarnib: given orally
|
Group 1 Phase II Sorafenib and Erlotinib
n=19 participants at risk
Patients receive oral sorafenib tosylate twice daily and oral erlotinib hydrochloride once daily on days 1-28.
sorafenib tosylate: given orally
erlotinib hydrochloride: given orally
|
Group 2 Phase II Sorafenib and Temsirolimus
n=18 participants at risk
Patients receive sorafenib tosylate 400 mg BID as in group 2. Patients also receive temsirolimus IV 25 mg over 30 minutes on days 1, 8, 15, and 22.
sorafenib tosylate: given orally
temsirolimus: IV administration
|
|---|---|---|---|---|---|
|
Nervous system disorders
Headache
|
0.00%
0/16 • 2 years
CTCAE
|
7.7%
1/13 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Gastrointestinal disorders
Acidosis
|
0.00%
0/16 • 2 years
CTCAE
|
7.7%
1/13 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Investigations
Alanine aminotransferase increased
|
18.8%
3/16 • Number of events 3 • 2 years
CTCAE
|
15.4%
2/13 • Number of events 2 • 2 years
CTCAE
|
8.3%
2/24 • Number of events 2 • 2 years
CTCAE
|
15.8%
3/19 • Number of events 3 • 2 years
CTCAE
|
16.7%
3/18 • Number of events 3 • 2 years
CTCAE
|
|
Investigations
Alkaline phosphatase increased
|
6.2%
1/16 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
12.5%
2/16 • Number of events 2 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/16 • 2 years
CTCAE
|
30.8%
4/13 • Number of events 4 • 2 years
CTCAE
|
12.5%
3/24 • Number of events 3 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
22.2%
4/18 • Number of events 4 • 2 years
CTCAE
|
|
Metabolism and nutrition disorders
Anorexia
|
6.2%
1/16 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
10.5%
2/19 • Number of events 2 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.2%
1/16 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
5.6%
1/18 • Number of events 1 • 2 years
CTCAE
|
|
Investigations
Aspartate aminotransferase increased
|
25.0%
4/16 • Number of events 4 • 2 years
CTCAE
|
15.4%
2/13 • Number of events 2 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/16 • 2 years
CTCAE
|
15.4%
2/13 • Number of events 2 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Skin and subcutaneous tissue disorders
Bruising
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
General disorders
Chills
|
0.00%
0/16 • 2 years
CTCAE
|
7.7%
1/13 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Investigations
Cholesterol high
|
0.00%
0/16 • 2 years
CTCAE
|
23.1%
3/13 • Number of events 3 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
27.8%
5/18 • Number of events 5 • 2 years
CTCAE
|
|
Psychiatric disorders
Confusion
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/16 • 2 years
CTCAE
|
15.4%
2/13 • Number of events 2 • 2 years
CTCAE
|
12.5%
3/24 • Number of events 3 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/16 • 2 years
CTCAE
|
7.7%
1/13 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Psychiatric disorders
Depression
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
5.6%
1/18 • Number of events 1 • 2 years
CTCAE
|
|
Gastrointestinal disorders
Diarrhea
|
25.0%
4/16 • Number of events 4 • 2 years
CTCAE
|
30.8%
4/13 • Number of events 4 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
10.5%
2/19 • Number of events 2 • 2 years
CTCAE
|
11.1%
2/18 • Number of events 2 • 2 years
CTCAE
|
|
Nervous system disorders
Dizziness
|
6.2%
1/16 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
6.2%
1/16 • Number of events 1 • 2 years
CTCAE
|
15.4%
2/13 • Number of events 2 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
5.6%
1/18 • Number of events 1 • 2 years
CTCAE
|
|
Gastrointestinal disorders
Dyspepsia
|
6.2%
1/16 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Ear and labyrinth disorders
Ear and labyrinth disorders - Other, specify
|
6.2%
1/16 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
General disorders
Fatigue
|
18.8%
3/16 • Number of events 3 • 2 years
CTCAE
|
15.4%
2/13 • Number of events 2 • 2 years
CTCAE
|
29.2%
7/24 • Number of events 7 • 2 years
CTCAE
|
31.6%
6/19 • Number of events 6 • 2 years
CTCAE
|
16.7%
3/18 • Number of events 3 • 2 years
CTCAE
|
|
Musculoskeletal and connective tissue disorders
Generalized Muscle Weakness
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Renal and urinary disorders
Hemoglobinuria
|
0.00%
0/16 • 2 years
CTCAE
|
7.7%
1/13 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
0.00%
0/16 • 2 years
CTCAE
|
7.7%
1/13 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
12.5%
2/16 • Number of events 2 • 2 years
CTCAE
|
7.7%
1/13 • Number of events 1 • 2 years
CTCAE
|
20.8%
5/24 • Number of events 5 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
16.7%
3/18 • Number of events 3 • 2 years
CTCAE
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
5.6%
1/18 • Number of events 1 • 2 years
CTCAE
|
|
Metabolism and nutrition disorders
Hypernatremia
|
0.00%
0/16 • 2 years
CTCAE
|
7.7%
1/13 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Vascular disorders
Hypertension
|
12.5%
2/16 • Number of events 2 • 2 years
CTCAE
|
7.7%
1/13 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
5.6%
1/18 • Number of events 1 • 2 years
CTCAE
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
0.00%
0/16 • 2 years
CTCAE
|
30.8%
4/13 • Number of events 4 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
22.2%
4/18 • Number of events 4 • 2 years
CTCAE
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
12.5%
2/16 • Number of events 2 • 2 years
CTCAE
|
7.7%
1/13 • Number of events 1 • 2 years
CTCAE
|
8.3%
2/24 • Number of events 2 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
6.2%
1/16 • Number of events 1 • 2 years
CTCAE
|
7.7%
1/13 • Number of events 1 • 2 years
CTCAE
|
20.8%
5/24 • Number of events 5 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
16.7%
3/18 • Number of events 3 • 2 years
CTCAE
|
|
Metabolism and nutrition disorders
Hypokalemia
|
18.8%
3/16 • Number of events 3 • 2 years
CTCAE
|
7.7%
1/13 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
11.1%
2/18 • Number of events 2 • 2 years
CTCAE
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
11.1%
2/18 • Number of events 2 • 2 years
CTCAE
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/16 • 2 years
CTCAE
|
7.7%
1/13 • Number of events 1 • 2 years
CTCAE
|
8.3%
2/24 • Number of events 2 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
5.6%
1/18 • Number of events 1 • 2 years
CTCAE
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
25.0%
4/16 • Number of events 4 • 2 years
CTCAE
|
23.1%
3/13 • Number of events 3 • 2 years
CTCAE
|
8.3%
2/24 • Number of events 2 • 2 years
CTCAE
|
15.8%
3/19 • Number of events 3 • 2 years
CTCAE
|
22.2%
4/18 • Number of events 4 • 2 years
CTCAE
|
|
Investigations
Lipase increased
|
31.2%
5/16 • Number of events 5 • 2 years
CTCAE
|
7.7%
1/13 • Number of events 1 • 2 years
CTCAE
|
16.7%
4/24 • Number of events 4 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Infections and infestations
Lung infection
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
5.6%
1/18 • Number of events 1 • 2 years
CTCAE
|
|
Investigations
Lymphocyte count decreased
|
12.5%
2/16 • Number of events 2 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
16.7%
4/24 • Number of events 4 • 2 years
CTCAE
|
15.8%
3/19 • Number of events 3 • 2 years
CTCAE
|
27.8%
5/18 • Number of events 5 • 2 years
CTCAE
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, specify
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Gastrointestinal disorders
Muscositis oral
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
16.7%
3/18 • Number of events 3 • 2 years
CTCAE
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Infections and infestations
Nail infection
|
6.2%
1/16 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Skin and subcutaneous tissue disorders
Nail loss
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
5.6%
1/18 • Number of events 1 • 2 years
CTCAE
|
|
Gastrointestinal disorders
Nausea
|
12.5%
2/16 • Number of events 2 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
8.3%
2/24 • Number of events 2 • 2 years
CTCAE
|
10.5%
2/19 • Number of events 2 • 2 years
CTCAE
|
11.1%
2/18 • Number of events 2 • 2 years
CTCAE
|
|
Investigations
Neutrophil count decreased
|
12.5%
2/16 • Number of events 2 • 2 years
CTCAE
|
7.7%
1/13 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Gastrointestinal disorders
Oral pain
|
6.2%
1/16 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome
|
12.5%
2/16 • Number of events 2 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
10.5%
2/19 • Number of events 2 • 2 years
CTCAE
|
5.6%
1/18 • Number of events 1 • 2 years
CTCAE
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
5.6%
1/18 • Number of events 1 • 2 years
CTCAE
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal mucositis
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
5.6%
1/18 • Number of events 1 • 2 years
CTCAE
|
|
Investigations
Platelet count decreased
|
18.8%
3/16 • Number of events 3 • 2 years
CTCAE
|
38.5%
5/13 • Number of events 5 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
10.5%
2/19 • Number of events 2 • 2 years
CTCAE
|
38.9%
7/18 • Number of events 7 • 2 years
CTCAE
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
12.5%
2/16 • Number of events 2 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
5.6%
1/18 • Number of events 1 • 2 years
CTCAE
|
|
Skin and subcutaneous tissue disorders
Purpura
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
5.6%
1/18 • Number of events 1 • 2 years
CTCAE
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
12.5%
2/16 • Number of events 2 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
25.0%
4/16 • Number of events 4 • 2 years
CTCAE
|
15.4%
2/13 • Number of events 2 • 2 years
CTCAE
|
8.3%
2/24 • Number of events 2 • 2 years
CTCAE
|
26.3%
5/19 • Number of events 5 • 2 years
CTCAE
|
16.7%
3/18 • Number of events 3 • 2 years
CTCAE
|
|
Investigations
Serum amylase increased
|
12.5%
2/16 • Number of events 2 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
1/16 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Eye disorders
Watering eyes
|
6.2%
1/16 • Number of events 1 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
0.00%
0/19 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Investigations
Weight loss
|
0.00%
0/16 • 2 years
CTCAE
|
0.00%
0/13 • 2 years
CTCAE
|
0.00%
0/24 • 2 years
CTCAE
|
10.5%
2/19 • Number of events 2 • 2 years
CTCAE
|
0.00%
0/18 • 2 years
CTCAE
|
|
Investigations
White blood cell count decreased
|
37.5%
6/16 • Number of events 6 • 2 years
CTCAE
|
23.1%
3/13 • Number of events 3 • 2 years
CTCAE
|
12.5%
3/24 • Number of events 3 • 2 years
CTCAE
|
5.3%
1/19 • Number of events 1 • 2 years
CTCAE
|
5.6%
1/18 • Number of events 1 • 2 years
CTCAE
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60