Trial Outcomes & Findings for Trial for Locally Advanced Breast Cancer Using Vorinostat Plus Chemotherapy (NCT NCT00574587)
NCT ID: NCT00574587
Last Updated: 2020-10-14
Results Overview
Dose limiting toxicity in cycle 1
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
55 participants
Primary outcome timeframe
3 weeks
Results posted on
2020-10-14
Participant Flow
Dates of recruitment: April 2008 - September 2013
Patients with HER2 positive disease also received trastuzumab.
Participant milestones
| Measure |
Stratum A (HER2-positive): Dose Level 1
Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery
Vorinostat: Vorinostat 200 mg PO BID on days 1-3 of each weekly paclitaxel dose
Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks
Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
Surgery: Surgical excision of tumor from breast
|
Stratum A (HER2-positive): Dose Level 2
Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery
Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose
Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks
Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
Surgery: Surgical excision of tumor from breast
|
Stratum B: Triple Negative
Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery
Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose
Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks
Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
Surgery: Surgical excision of tumor from breast
|
Stratum C: ER-Positive, HER2-negative
Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery
Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose
Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks
Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
Surgery: Surgical excision of tumor from breast
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
23
|
16
|
13
|
|
Overall Study
COMPLETED
|
3
|
23
|
16
|
13
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Trial for Locally Advanced Breast Cancer Using Vorinostat Plus Chemotherapy
Baseline characteristics by cohort
| Measure |
Stratum A (HER2-positive): Dose Level 1
n=3 Participants
Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery
Vorinostat: Vorinostat 200 mg PO BID on days 1-3 of each weekly paclitaxel dose
Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks
Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
Surgery: Surgical excision of tumor from breast
|
Stratum A (HER2-positive): Dose Level 2
n=23 Participants
Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery
Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose
Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks
Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
Surgery: Surgical excision of tumor from breast
|
Stratum B: Triple Negative
n=16 Participants
Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery
Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose
Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks
Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
Surgery: Surgical excision of tumor from breast
|
Stratum C: ER-Positive, HER2-Negative
n=13 Participants
Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery
Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose
Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks
Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
Surgery: Surgical excision of tumor from breast
|
Total
n=55 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
54 years
n=99 Participants
|
54 years
n=107 Participants
|
48 years
n=206 Participants
|
46 years
n=7 Participants
|
52 years
n=31 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
13 Participants
n=7 Participants
|
55 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
PRIMARY outcome
Timeframe: 3 weeksPopulation: The recommended Phase II Dose of vorinostat was determined in Stratum A and B participants only.
Dose limiting toxicity in cycle 1
Outcome measures
| Measure |
Stratum A: VR-Paclitaxel-Trastuzumab
n=6 Participants
Stratum A: Vorinostat 200 (Dose Level 1) or 300 mg (Dose level 2) by mouth on days 1-3 plus weekly paclitaxel 80 mg x 12 weeks and trastuzumab 4 mg/kg, then 2 mg/kg x 12 weeks, followed by doxorubicin 60 mg/m2 -cyclophosphamide 600 mg/m2 every 2 weeks x 8 weeks, followed by surgery
|
Stratum B: VR-Paclitaxel-Trastuzumab
n=6 Participants
Stratum B: 300 mg by mouth on days 1-3 plus weekly paclitaxel 80 mg x 12 weeks and trastuzumab 4 mg/kg, then 2 mg/kg x 12 weeks, followed by doxorubicin 60 mg/m2 -cyclophosphamide 600 mg/m2 every 2 weeks x 8 weeks, followed by surgery
|
Stratum C: ER-Positive, HER2-negative
Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery
Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose
Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks
Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
Surgery: Surgical excision of tumor from breast
|
|---|---|---|---|
|
Recommended Phase II Dose of Vorinostat in Combination With Weekly Paclitaxel/Trastuzumab
|
300 mg
|
300 mg
|
—
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Stratum A (HER2-positive): Dose Level 1 and Stratum A (HER2-positive): Dose Level 2 are combined. Data was collected for outcome measures per stratum not per dose level. 2 pts in Stratum A were not evaluable (1 lost to f/u; 1 death); 1 pt was not evaluable in Stratum B (1 death) and 1 pt was not evaluable in C (1 declined surgery)
Pathological Complete Response (CR) defined as absence of invasive cancer at surgery
Outcome measures
| Measure |
Stratum A: VR-Paclitaxel-Trastuzumab
n=24 Participants
Stratum A: Vorinostat 200 (Dose Level 1) or 300 mg (Dose level 2) by mouth on days 1-3 plus weekly paclitaxel 80 mg x 12 weeks and trastuzumab 4 mg/kg, then 2 mg/kg x 12 weeks, followed by doxorubicin 60 mg/m2 -cyclophosphamide 600 mg/m2 every 2 weeks x 8 weeks, followed by surgery
|
Stratum B: VR-Paclitaxel-Trastuzumab
n=15 Participants
Stratum B: 300 mg by mouth on days 1-3 plus weekly paclitaxel 80 mg x 12 weeks and trastuzumab 4 mg/kg, then 2 mg/kg x 12 weeks, followed by doxorubicin 60 mg/m2 -cyclophosphamide 600 mg/m2 every 2 weeks x 8 weeks, followed by surgery
|
Stratum C: ER-Positive, HER2-negative
n=12 Participants
Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery
Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose
Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks
Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
Surgery: Surgical excision of tumor from breast
|
|---|---|---|---|
|
Pathological Complete Response (CR) Rate in Patients With Her2/Neu Positive Locally Advanced Breast Cancer.
|
13 Participants
|
4 Participants
|
0 Participants
|
Adverse Events
Stratum A (HER2-positive): Dose Level 1
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Stratum A (HER2-positive): Dose Level 2
Serious events: 2 serious events
Other events: 0 other events
Deaths: 1 deaths
Stratum B: Triple Negative
Serious events: 1 serious events
Other events: 0 other events
Deaths: 1 deaths
Stratum C: ER-Positive, HER2-negative
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Stratum A (HER2-positive): Dose Level 1
n=3 participants at risk
Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery
Vorinostat: Vorinostat 200 mg PO BID on days 1-3 of each weekly paclitaxel dose
Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks
Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
Surgery: Surgical excision of tumor from breast
|
Stratum A (HER2-positive): Dose Level 2
n=23 participants at risk
Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery
Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose
Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks
Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
Surgery: Surgical excision of tumor from breast
|
Stratum B: Triple Negative
n=16 participants at risk
Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery
Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose
Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks
Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
Surgery: Surgical excision of tumor from breast
|
Stratum C: ER-Positive, HER2-negative
n=13 participants at risk
Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery
Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose
Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks
Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
Surgery: Surgical excision of tumor from breast
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
pulmonary emobolism
|
0.00%
0/3
|
4.3%
1/23 • Number of events 1
|
0.00%
0/16
|
0.00%
0/13
|
|
Cardiac disorders
cardiac tamponade
|
0.00%
0/3
|
0.00%
0/23
|
6.2%
1/16 • Number of events 1
|
0.00%
0/13
|
|
Cardiac disorders
congestive heart failure
|
0.00%
0/3
|
4.3%
1/23 • Number of events 1
|
0.00%
0/16
|
0.00%
0/13
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place