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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01271803




Registration number
NCT01271803
Ethics application status
Date submitted
5/01/2011
Date registered
7/01/2011
Date last updated
29/07/2019

Titles & IDs
Public title
A Study of Vemurafenib and GDC-0973 (Cobimetinib) in Participants With BRAFV600E Mutation-Positive Metastatic Melanoma
Scientific title
A Phase IB, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability and Pharmacokinetics of Vemurafenib in Combination With GDC-0973 (Cobimetinib) When Administered in BRAFV600E Mutation-Positive Patients Previously Treated (But Without Prior Exposure to BRAF or MEK Inhibitor Therapy) or Previously Untreated for Locally Advanced/Unresectable or Metastatic Melanoma or Those Who Have Progressed After Treatment With Vemurafenib
Secondary ID [1] 0 0
NO25395
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cobimetinib
Treatment: Drugs - vemurafenib

Experimental: DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib - Participants will receive oral 60 milligrams (mg) cobimetinib once daily (QD) on Days 1-14, followed by 14 days off on Days 15-28 (14/14 dosing schedule) and oral 720 mg vemurafenib twice daily (BID) on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Experimental: DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib - Participants will receive oral 60 mg cobimetinib QD on Days 1-21, followed by 7 days off on Days 22-28 (21/7 dosing schedule) and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Experimental: DES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib - Participants will receive oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Experimental: DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib - Participants will receive oral 60 mg cobimetinib QD on Days 1-28 (28/0 dosing schedule) and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Experimental: DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib - Participants will receive oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Experimental: DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib - Participants will receive oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Experimental: DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib - Participants will receive oral 100 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Experimental: DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib - Participants will receive oral 60 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Experimental: DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib - Participants will receive oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Experimental: Cobimetinib Monotherapy (100 mg or 60 mg) - Participants will receive oral 60 mg cobimetinib QD on 21/7 dosing schedule, or oral 100 mg cobimetinib QD on 14/14 dosing schedule of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Experimental: CES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib - Participants will receive oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Experimental: CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib - Participants will receive oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.


Treatment: Drugs: Cobimetinib
Participants will receive cobimetinib 60 to 100 mg at any of the 3 dosing schedules with or without vemurafenib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Treatment: Drugs: vemurafenib
Participants will receive vemurafenib 720 or 960 mg along with cobimetinib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Dose-Limiting Toxicities (DLTs) During DES in Combination Cohorts
Timepoint [1] 0 0
28 Days
Primary outcome [2] 0 0
Maximum Tolerated Doses (MTD) of Vemurafenib and Cobimetinib When Administered in Combination in DES
Timepoint [2] 0 0
28 Days
Primary outcome [3] 0 0
Maximum Plasma Concentration (Cmax) of Cobimetinib on Day 1, Cycle 1
Timepoint [3] 0 0
Cycle 1: predose (0 hours [hr]) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1
Primary outcome [4] 0 0
Cmax of Cobimetinib on Day 1, Cycle 1 in Cohort 3
Timepoint [4] 0 0
Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1
Primary outcome [5] 0 0
Time Taken to Reach Maximum Plasma Concentration (Tmax) of Cobimetinib on Day 1, Cycle 1
Timepoint [5] 0 0
Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1
Primary outcome [6] 0 0
Area Under Concentration Versus Time Curve (AUC) Over a Period of 24 Hours (AUC0-24) of Cobimetinib on Day 1, Cycle 1
Timepoint [6] 0 0
Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1
Primary outcome [7] 0 0
AUC0-24 of Cobimetinib on Day 1, Cycle 1 of Cohort 3
Timepoint [7] 0 0
Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1
Primary outcome [8] 0 0
Cmax of Cobimetinib on Day 14 (Steady State), Cycle 1
Timepoint [8] 0 0
Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14
Primary outcome [9] 0 0
Tmax of Cobimetinib on Day 14 (Steady State), Cycle 1
Timepoint [9] 0 0
Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14
Primary outcome [10] 0 0
AUC0-24 of Cobimetinib on Day 14, Cycle 1
Timepoint [10] 0 0
Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14
Primary outcome [11] 0 0
Clearance (CL) of Cobimetinib on Day 14 (Steady State), Cycle 1
Timepoint [11] 0 0
Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14
Primary outcome [12] 0 0
Cmax of Vemurafenib on Day -1, Cycle 1 in Participants Previously Treated With Vemurafenib Prior to Enrollment Into This Study
Timepoint [12] 0 0
Predose (0 hr) on Days -1, 1; 2, 4, 6, 8 hr postdose on Day -1
Primary outcome [13] 0 0
Cmax of Vemurafenib on Day -1, Cycle 1 of Cohorts 1C and 2A in Participants Previously Treated With Vemurafenib Prior to Enrollment Into This Study
Timepoint [13] 0 0
Predose (0 hr) on Day -1, 1; 2, 4, 6, 8 hr postdose on Day -1
Primary outcome [14] 0 0
Tmax of Vemurafenib on Day -1, Cycle 1 in Participants Previously Treated With Vemurafenib Prior to Enrollment Into This Study
Timepoint [14] 0 0
Predose (0 hr) on Day -1, 1; 2, 4, 6, 8 hr postdose on Day -1
Primary outcome [15] 0 0
Cmax of Vemurafenib on Day 1, Cycle 1 in BRAFi-naïve Participants
Timepoint [15] 0 0
Predose (0 hr) on Day 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1
Primary outcome [16] 0 0
Cmax of Vemurafenib on Day 1, Cycle 1 in Cohort 1A in BRAFi-naïve Participants
Timepoint [16] 0 0
Predose (0 hr) on Day 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1
Primary outcome [17] 0 0
Tmax of Vemurafenib on Day 1, Cycle 1 in BRAFi-naïve Participants
Timepoint [17] 0 0
Predose (0 hr) on Day 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1
Primary outcome [18] 0 0
Cmax of Vemurafenib on Day 14, Cycle 1
Timepoint [18] 0 0
Predose (0 hr) on Days 14, 15; 0.5, 1, 2, 4, 6, 8 hr postdose on Day 14
Primary outcome [19] 0 0
Tmax of Vemurafenib on Day 14, Cycle 1
Timepoint [19] 0 0
Predose (0 hr) on Days 14, 15; 0.5, 1, 2, 4, 6, 8 hr postdose on Day 14
Secondary outcome [1] 0 0
Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version (V) 1.1
Timepoint [1] 0 0
Assessed at screening (within 28 days prior to initiation of Cycle 1), every 6 weeks thereafter until disease progression (up to 82 months)
Secondary outcome [2] 0 0
Percentage of Participants With Disease Progression According to RECIST V 1.1
Timepoint [2] 0 0
Assessed at screening (within 28 days prior to initiation of Cycle 1), every 6 weeks thereafter until disease progression or death (up to 82 months)
Secondary outcome [3] 0 0
Median Duration of Response (DOR)
Timepoint [3] 0 0
Time from first occurrence of objective response until the time of disease progression or death from any cause (up to 82 months)
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
Assessed at screening (within 28 days prior to initiation of Cycle 1), every 6 weeks thereafter until disease progression or death (up to 82 months)
Secondary outcome [5] 0 0
Average Percent Change From Baseline in Fluorodeoxyglucose-positron Emission Tomography (FDG-PET) at Cycle 1 and Cycle 2
Timepoint [5] 0 0
Cycle 1 (Days 10 to 14), Cycle 2 (Days 14+7)
Secondary outcome [6] 0 0
Pharmacodynamics: Number of Participants With Mitogen-Activated Protein Kinase (MAPK) Inhibition, as Assessed by Immunohistochemistry (IHC)
Timepoint [6] 0 0
At baseline; Cycle 1: Day 14; at disease progression (Up to 32 months)

Eligibility
Key inclusion criteria
* Participants with histologically confirmed melanoma (unresectable Stage IIIc and Stage IV metastatic melanoma, as defined by American Joint Committee on Cancer [AJCC])
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version (V) 1.1
* Eastern Cooperative Oncology Group (ECOG) Performance Status of less than or equal to (</=) 1
* Participants must

1. be previously untreated for locally advanced/unresectable or metastatic melanoma or
2. previously treated but without prior exposure to any BRAF or MEK inhibitor therapy or
3. progressed on vemurafenib while participating in a Phase I (including clinical pharmacology studies), II, or III clinical study or expanded access programs (EAP) immediately prior to enrollment in this study or
4. progressed on vemurafenib administered in a postmarketing setting immediately prior to enrollment in this study.
* Life expectancy >/=12 weeks
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History of prior significant toxicity from another RAF or MEK pathway inhibitor requiring discontinuation of treatment
* Palliative radiotherapy within 2 weeks prior to first dose of study drug treatment
* Experimental therapy within 4 weeks prior to first dose of study drug treatment except vemurafenib
* Major surgery within 4 weeks of first dose of study drug treatment or planning a major surgery during the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter Maccallum Cancer Institute; Medical Oncology - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.