Trial Outcomes & Findings for Gamma-secretase/Notch Signalling Pathway Inhibitor RO4929097 in Combination With Cisplatin, Vinblastine, and Temozolomide in Treating Patients With Recurrent or Metastatic Melanoma (NCT NCT01196416)
NCT ID: NCT01196416
Last Updated: 2019-11-18
Results Overview
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression
COMPLETED
PHASE1/PHASE2
14 participants
From the time measurement criteria are met for CR or PR until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years
2019-11-18
Participant Flow
Participant milestones
| Measure |
Treatment (RO4929097, Cisplatin, Vinblastine, Temozolomide)
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097, vinblastine and temozolomide
|
|---|---|
|
Overall Study
STARTED
|
14
|
|
Overall Study
COMPLETED
|
12
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Treatment (RO4929097, Cisplatin, Vinblastine, Temozolomide)
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097, vinblastine and temozolomide
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
Baseline Characteristics
Gamma-secretase/Notch Signalling Pathway Inhibitor RO4929097 in Combination With Cisplatin, Vinblastine, and Temozolomide in Treating Patients With Recurrent or Metastatic Melanoma
Baseline characteristics by cohort
| Measure |
Treatment (RO4929097, Cisplatin, Vinblastine, Temozolomide)
n=14 Participants
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097, vinblastine and temozolomide
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
7 Participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: From the time measurement criteria are met for CR or PR until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 yearsPer Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression
Outcome measures
| Measure |
Treatment (RO4929097, Cisplatin, Vinblastine, Temozolomide)
n=12 Participants
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097, vinblastine and temozolomide
|
|---|---|
|
Overall Objective Response
Partial Response (PR)
|
3 Participants
|
|
Overall Objective Response
Stable Disease (SD)
|
3 Participants
|
|
Overall Objective Response
Progression of Disease (POD)
|
6 Participants
|
PRIMARY outcome
Timeframe: 21 daysbased on the incidence of dose-limiting toxicity as assessed the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase IB) Data is not yet available, as it's currently being analyzed.
Outcome measures
| Measure |
Treatment (RO4929097, Cisplatin, Vinblastine, Temozolomide)
n=14 Participants
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097, vinblastine and temozolomide
|
|---|---|
|
Maximum-tolerated Dose for Cisplatin, Vinblastine and TMZ
Cisplatin
|
20 mg/m2
|
|
Maximum-tolerated Dose for Cisplatin, Vinblastine and TMZ
Vinblastine
|
1.2 mg/m2
|
|
Maximum-tolerated Dose for Cisplatin, Vinblastine and TMZ
Temozolomide
|
150 mg/m2
|
PRIMARY outcome
Timeframe: Up to 2 yearsOverall response rate (complete \[CR\] or partial response \[PR\]) according to RECIST version 1.1
Outcome measures
| Measure |
Treatment (RO4929097, Cisplatin, Vinblastine, Temozolomide)
n=14 Participants
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097, vinblastine and temozolomide
|
|---|---|
|
Overall Survival (Phase II)
Partial Response
|
3 participants
|
|
Overall Survival (Phase II)
Stable Disease
|
5 participants
|
|
Overall Survival (Phase II)
Progression of Disease
|
6 participants
|
PRIMARY outcome
Timeframe: 21 daysbased on the incidence of dose-limiting toxicity as assessed the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase IB)
Outcome measures
| Measure |
Treatment (RO4929097, Cisplatin, Vinblastine, Temozolomide)
n=14 Participants
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097, vinblastine and temozolomide
|
|---|---|
|
Maximum Tolerated Dose for RO4929097
|
15 mg/day
|
SECONDARY outcome
Timeframe: Baseline up to 2 weeksParticipants' pre and post-treatment protein levels will be compared
Outcome measures
| Measure |
Treatment (RO4929097, Cisplatin, Vinblastine, Temozolomide)
n=5 Participants
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097, vinblastine and temozolomide
|
|---|---|
|
Participants' Change in Protein Levels
decrease in post-treatment cleaved notch protein
|
4 Participants
|
|
Participants' Change in Protein Levels
no change
|
1 Participants
|
SECONDARY outcome
Timeframe: Days 4 and 5Outcome measures
| Measure |
Treatment (RO4929097, Cisplatin, Vinblastine, Temozolomide)
n=5 Participants
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097, vinblastine and temozolomide
|
|---|---|
|
Cycle 1 AUC/Pharmacokinetics of Gamma-secretase Inhibitor RO4929097 in Combination With Temozolomide (Phase IB)
|
5410 hr·ng/mL
Standard Deviation 3355
|
SECONDARY outcome
Timeframe: At Cycle 1Outcome measures
| Measure |
Treatment (RO4929097, Cisplatin, Vinblastine, Temozolomide)
n=5 Participants
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097, vinblastine and temozolomide
|
|---|---|
|
Cycle 1 C Max/Pharmacokinetics of Gamma-secretase Inhibitor RO4929097 in Combination With Temozolomide (Phase IB)
|
301 ng/mL
Standard Deviation 172
|
SECONDARY outcome
Timeframe: At Day 2 of Cycle 1Outcome measures
| Measure |
Treatment (RO4929097, Cisplatin, Vinblastine, Temozolomide)
n=5 Participants
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097, vinblastine and temozolomide
|
|---|---|
|
Cycle 1 Mean Day 2 Trough/Pharmacokinetics of Gamma-secretase Inhibitor RO4929097 in Combination With Temozolomide (Phase IB)
|
129 ng/mL
Standard Deviation 88
|
SECONDARY outcome
Timeframe: 2 weeksThe association of response or clinical benefit with the presence or absence of markers of pathway inhibition in patient tumors will be tested using Fisher's exact test.
Outcome measures
| Measure |
Treatment (RO4929097, Cisplatin, Vinblastine, Temozolomide)
n=5 Participants
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097, vinblastine and temozolomide
|
|---|---|
|
Number of Participants With Presence or Absence of Markers of Notch Signalling Pathway Inhibition in Patient Tumors (Phase Ib)
Insufficient tissue to asses any change
|
1 Participants
|
|
Number of Participants With Presence or Absence of Markers of Notch Signalling Pathway Inhibition in Patient Tumors (Phase Ib)
Sig decrease in post-treatment cleaved Notch
|
4 Participants
|
SECONDARY outcome
Timeframe: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 2 yearsProgression-free survival curves will be generated using Kaplan-Meier methodology.
Outcome measures
| Measure |
Treatment (RO4929097, Cisplatin, Vinblastine, Temozolomide)
n=14 Participants
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097, vinblastine and temozolomide
|
|---|---|
|
Progression-free Survival (Phase II)
|
2.7 months
Interval 1.2 to 4.1
|
SECONDARY outcome
Timeframe: Up to 30 days post-treatmentNumber of patients with AE's as assessed by NCI CTCAE v. 4.0 Please see Adverse Events section for specifics.
Outcome measures
| Measure |
Treatment (RO4929097, Cisplatin, Vinblastine, Temozolomide)
n=14 Participants
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097, vinblastine and temozolomide
|
|---|---|
|
Participants Evaluated for Toxicity
|
14 Participants
|
Adverse Events
Treatment (RO4929097, Cisplatin, Vinblastine, Temozolomide)
Serious adverse events
| Measure |
Treatment (RO4929097, Cisplatin, Vinblastine, Temozolomide)
n=14 participants at risk
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097, vinblastine and temozolomide
|
|---|---|
|
Renal and urinary disorders
Acute kidney injury
|
7.1%
1/14
|
|
Blood and lymphatic system disorders
Alanine aminotransferase increased
|
7.1%
1/14
|
|
Blood and lymphatic system disorders
Anemia
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Creatinine increased
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Hyponatremia
|
14.3%
2/14
|
|
Infections and infestations
Infections and infestations
|
7.1%
1/14
|
|
Blood and lymphatic system disorders
Lymphocyte count decreased
|
28.6%
4/14
|
|
Blood and lymphatic system disorders
Neutrophil count decreased
|
35.7%
5/14
|
|
General disorders
Pain
|
7.1%
1/14
|
|
Musculoskeletal and connective tissue disorders
Spinal fracture
|
7.1%
1/14
|
|
Blood and lymphatic system disorders
White blood cell decreased
|
28.6%
4/14
|
Other adverse events
| Measure |
Treatment (RO4929097, Cisplatin, Vinblastine, Temozolomide)
n=14 participants at risk
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097, vinblastine and temozolomide
|
|---|---|
|
Blood and lymphatic system disorders
Alanine aminotransferase increased
|
28.6%
4/14
|
|
Metabolism and nutrition disorders
Alkaline phosphatase increased
|
14.3%
2/14
|
|
Blood and lymphatic system disorders
Anemia
|
78.6%
11/14
|
|
General disorders
Anorexia
|
7.1%
1/14
|
|
Blood and lymphatic system disorders
Aspartate aminotransferase increased
|
14.3%
2/14
|
|
Metabolism and nutrition disorders
Blood bilirubin increased
|
14.3%
2/14
|
|
Blood and lymphatic system disorders
CPK increased
|
7.1%
1/14
|
|
Gastrointestinal disorders
Constipation
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Creatinine increased
|
28.6%
4/14
|
|
Gastrointestinal disorders
Diarrhea
|
7.1%
1/14
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
7.1%
1/14
|
|
General disorders
Fatigue
|
28.6%
4/14
|
|
General disorders
Flank pain
|
14.3%
2/14
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
85.7%
12/14
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
28.6%
4/14
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
7.1%
1/14
|
|
Cardiac disorders
Hypertension
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
64.3%
9/14
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
78.6%
11/14
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
14.3%
2/14
|
|
Metabolism and nutrition disorders
Hypokalemia
|
28.6%
4/14
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Hyponatremia
|
42.9%
6/14
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
85.7%
12/14
|
|
Metabolism and nutrition disorders
Lipase increased
|
7.1%
1/14
|
|
Blood and lymphatic system disorders
Lymphocyte count decreased
|
71.4%
10/14
|
|
General disorders
Nausea
|
14.3%
2/14
|
|
General disorders
Neck pain
|
7.1%
1/14
|
|
Blood and lymphatic system disorders
Neutrophil count decreased
|
50.0%
7/14
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
14.3%
2/14
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
42.9%
6/14
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.1%
1/14
|
|
Blood and lymphatic system disorders
Serum amylase increased
|
7.1%
1/14
|
|
Cardiac disorders
Thromboembolic event
|
7.1%
1/14
|
|
Renal and urinary disorders
Urinary tract infection
|
14.3%
2/14
|
|
Blood and lymphatic system disorders
White blood cell decreased
|
64.3%
9/14
|
Additional Information
Dr. Mark Dickson
Memorial Sloan Kettering Cancer Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60