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Study of Cobimetinib in Participants With Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT00467779
First received: April 18, 2007
Last updated: July 25, 2016
Last verified: July 2016
Results First Received: June 10, 2016  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Solid Tumor
Interventions: Drug: cobimetinib
Drug: dextromethorphan
Drug: midazolam

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Study included following stages: Stage 1, Stage 1A, Stage 2, Stage 2A, and Stage 3. Different participants were recruited in each stage.

Reporting Groups
  Description
Stage 1 Cohort 01 – Cobimetinib 0.05 mg/kg (21/7) Participants received cobimetinib (GDC-0973/XL518) 0.05 milligrams per kilograms (mg/kg) via solution or capsule, once daily for Days 1-21 of each 28-day cycle (21 days on drug followed by 7 days off treatment [21/7 schedule]). Treatment was continued until progressive disease (PD) or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1 Cohort 02 – Cobimetinib 0.10 mg/kg (21/7) Participants received cobimetinib 0.10 mg/kg via solution or capsule, once daily for Days 1-21 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1 Cohort 03 – Cobimetinib 0.20 mg/kg (21/7) Participants received cobimetinib 0.20 mg/kg via solution or capsule, once daily for Days 1-21 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7) Participants received cobimetinib 10 mg via solution or capsule, once daily for Days 1-21 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7) Participants received cobimetinib 20 mg via solution or capsule, once daily for Days 1-21 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7) Participants received cobimetinib 40 mg via solution or capsule, once daily for Days 1-21 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1 Cohort 07 – Cobimetinib 60 mg (21/7) Participants received cobimetinib 60 mg via solution or capsule, once daily for Days 1-21 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7) Participants received cobimetinib 80 mg via solution or capsule, once daily for Days 1-21 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 2 Cohort 20 – Cobimetinib 60 mg (Expansion) (21/7) Participants received cobimetinib 60 mg via solution or capsule, once daily for Days 1-21 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14) Participants received cobimetinib 60 mg via solution or capsule, once daily for Days 1-14 of each 28-day cycle (14 days on drug followed by 14 days off treatment [14/14 schedule]). Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14) Participants received cobimetinib 80 mg via solution or capsule, once daily for Days 1-14 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14) Participants received cobimetinib 100 mg via solution or capsule, once daily for Days 1-14 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14) Participants received cobimetinib 125 mg via solution or capsule, once daily for Days 1-14 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 2A Cohort 30 - Cobimetinib 100 mg (Expansion) (14/14) Participants received cobimetinib 100 mg via solution or capsule, once daily for Days 1-14 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 3 Cohort 40 - Cobimetinib+Midazolam+Dextromethorphan Participants received a single dose of midazolam (2 mg of midazolam syrup) and dextromethorphan (30 mg tablet) on Cycle 1 Day 1, in the absence of cobimetinib. After a 2-day washout period, participants received 21 consecutive daily doses of cobimetinib (60-mg) followed by a 7-day washout period.Participants received another single dose of midazolam and dextromethorphan on Cycle 1 Day 15, in the presence of steady-state cobimetinib concentrations. In Cycle 2 and beyond received cobimetinib alone, administered as a 60-mg daily dose for 21 consecutive days in 28-day cycles.

Participant Flow for 5 periods

Period 1:   Stage 1
    Stage 1 Cohort 01 – Cobimetinib 0.05 mg/kg (21/7)     Stage 1 Cohort 02 – Cobimetinib 0.10 mg/kg (21/7)     Stage 1 Cohort 03 – Cobimetinib 0.20 mg/kg (21/7)     Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7)     Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7)     Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7)     Stage 1 Cohort 07 – Cobimetinib 60 mg (21/7)     Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7)     Stage 2 Cohort 20 – Cobimetinib 60 mg (Expansion) (21/7)     Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14)     Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14)     Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14)     Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14)     Stage 2A Cohort 30 - Cobimetinib 100 mg (Expansion) (14/14)     Stage 3 Cohort 40 - Cobimetinib+Midazolam+Dextromethorphan  
STARTED     4     3     3     3     3     6     7     7     0     0     0     0     0     0     0  
COMPLETED     0     0     0     0     0     1     0     0     0     0     0     0     0     0     0  
NOT COMPLETED     4     3     3     3     3     5     7     7     0     0     0     0     0     0     0  
Adverse Event                 1                 0                 0                 0                 0                 1                 2                 1                 0                 0                 0                 0                 0                 0                 0  
Disease Progression                 2                 2                 2                 3                 2                 2                 4                 5                 0                 0                 0                 0                 0                 0                 0  
Unspecified Reason                 1                 0                 1                 0                 1                 2                 0                 0                 0                 0                 0                 0                 0                 0                 0  
Physician Decision                 0                 1                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0  
Withdrawal by Subject                 0                 0                 0                 0                 0                 0                 1                 1                 0                 0                 0                 0                 0                 0                 0  

Period 2:   Stage 1A
    Stage 1 Cohort 01 – Cobimetinib 0.05 mg/kg (21/7)     Stage 1 Cohort 02 – Cobimetinib 0.10 mg/kg (21/7)     Stage 1 Cohort 03 – Cobimetinib 0.20 mg/kg (21/7)     Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7)     Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7)     Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7)     Stage 1 Cohort 07 – Cobimetinib 60 mg (21/7)     Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7)     Stage 2 Cohort 20 – Cobimetinib 60 mg (Expansion) (21/7)     Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14)     Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14)     Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14)     Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14)     Stage 2A Cohort 30 - Cobimetinib 100 mg (Expansion) (14/14)     Stage 3 Cohort 40 - Cobimetinib+Midazolam+Dextromethorphan  
STARTED     0     0     0     0     0     0     0     0     0     3     3     8     6     0     0  
COMPLETED     0     0     0     0     0     0     0     0     0     0     0     0     0     0     0  
NOT COMPLETED     0     0     0     0     0     0     0     0     0     3     3     8     6     0     0  
Adverse Event                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1                 0                 0  
Death                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1                 1                 0                 0  
Disease Progression                 0                 0                 0                 0                 0                 0                 0                 0                 0                 2                 2                 5                 2                 0                 0  
Physician Decision                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1                 0                 0                 0                 0                 0  
Withdrawal by Subject                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1                 1                 1                 0                 0  
Unspecified Reason                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1                 1                 0                 0  

Period 3:   Stage 2
    Stage 1 Cohort 01 – Cobimetinib 0.05 mg/kg (21/7)     Stage 1 Cohort 02 – Cobimetinib 0.10 mg/kg (21/7)     Stage 1 Cohort 03 – Cobimetinib 0.20 mg/kg (21/7)     Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7)     Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7)     Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7)     Stage 1 Cohort 07 – Cobimetinib 60 mg (21/7)     Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7)     Stage 2 Cohort 20 – Cobimetinib 60 mg (Expansion) (21/7)     Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14)     Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14)     Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14)     Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14)     Stage 2A Cohort 30 - Cobimetinib 100 mg (Expansion) (14/14)     Stage 3 Cohort 40 - Cobimetinib+Midazolam+Dextromethorphan  
STARTED     0     0     0     0     0     0     0     0     21     0     0     0     0     0     0  
COMPLETED     0     0     0     0     0     0     0     0     0     0     0     0     0     0     0  
NOT COMPLETED     0     0     0     0     0     0     0     0     21     0     0     0     0     0     0  
Adverse Event                 0                 0                 0                 0                 0                 0                 0                 0                 1                 0                 0                 0                 0                 0                 0  
Death                 0                 0                 0                 0                 0                 0                 0                 0                 1                 0                 0                 0                 0                 0                 0  
Disease Progression                 0                 0                 0                 0                 0                 0                 0                 0                 16                 0                 0                 0                 0                 0                 0  
Unspecified Reason                 0                 0                 0                 0                 0                 0                 0                 0                 3                 0                 0                 0                 0                 0                 0  

Period 4:   Stage 2A
    Stage 1 Cohort 01 – Cobimetinib 0.05 mg/kg (21/7)     Stage 1 Cohort 02 – Cobimetinib 0.10 mg/kg (21/7)     Stage 1 Cohort 03 – Cobimetinib 0.20 mg/kg (21/7)     Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7)     Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7)     Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7)     Stage 1 Cohort 07 – Cobimetinib 60 mg (21/7)     Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7)     Stage 2 Cohort 20 – Cobimetinib 60 mg (Expansion) (21/7)     Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14)     Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14)     Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14)     Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14)     Stage 2A Cohort 30 - Cobimetinib 100 mg (Expansion) (14/14)     Stage 3 Cohort 40 - Cobimetinib+Midazolam+Dextromethorphan  
STARTED     0     0     0     0     0     0     0     0     0     0     0     0     0     22     0  
COMPLETED     0     0     0     0     0     0     0     0     0     0     0     0     0     1     0  
NOT COMPLETED     0     0     0     0     0     0     0     0     0     0     0     0     0     21     0  
Adverse Event                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 2                 0  
Death                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1                 0  
Disease Progression                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 10                 0  
Unspecified Reason                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 7                 0  
Withdrawal by Subject                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1                 0  

Period 5:   Stage 3
    Stage 1 Cohort 01 – Cobimetinib 0.05 mg/kg (21/7)     Stage 1 Cohort 02 – Cobimetinib 0.10 mg/kg (21/7)     Stage 1 Cohort 03 – Cobimetinib 0.20 mg/kg (21/7)     Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7)     Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7)     Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7)     Stage 1 Cohort 07 – Cobimetinib 60 mg (21/7)     Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7)     Stage 2 Cohort 20 – Cobimetinib 60 mg (Expansion) (21/7)     Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14)     Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14)     Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14)     Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14)     Stage 2A Cohort 30 - Cobimetinib 100 mg (Expansion) (14/14)     Stage 3 Cohort 40 - Cobimetinib+Midazolam+Dextromethorphan  
STARTED     0     0     0     0     0     0     0     0     0     0     0     0     0     0     20  
COMPLETED     0     0     0     0     0     0     0     0     0     0     0     0     0     0     3  
NOT COMPLETED     0     0     0     0     0     0     0     0     0     0     0     0     0     0     17  
Adverse Event                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 2  
Death                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1  
Disease Progression                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 9  
Unspecified Reason                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 5  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population consisted of all participants who received at least 1 dose of study drug.

Reporting Groups
  Description
Stage 1 Cohort 01 – Cobimetinib 0.05 mg/kg (21/7) Participants received cobimetinib 0.05 mg/kg via solution or capsule, once daily for Days 1-21 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1 Cohort 02 – Cobimetinib 0.10 mg/kg (21/7) Participants received cobimetinib 0.10 mg/kg via solution or capsule, once daily for Days 1-21 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1 Cohort 03 – Cobimetinib 0.20 mg/kg (21/7) Participants received cobimetinib 0.20 mg/kg via solution or capsule, once daily for Days 1-21 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7) Participants received cobimetinib 10 mg via solution or capsule, once daily for Days 1-21 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7) Participants received cobimetinib 20 mg via solution or capsule, once daily for Days 1-21 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7) Participants received cobimetinib 40 mg via solution or capsule, once daily for Days 1-21 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1 Cohort 07 – Cobimetinib 60 mg (21/7) Participants received cobimetinib 60 mg via solution or capsule, once daily for Days 1-21 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7) Participants received cobimetinib 80 mg via solution or capsule, once daily for Days 1-21 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 2 Cohort 20 – Cobimetinib 60 mg (Expansion) (21/7) Participants received cobimetinib 60 mg via solution or capsule, once daily for Days 1-21 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14) Participants received cobimetinib 60 mg via solution or capsule, once daily for Days 1-14 of each 28-day cycle (14 days on drug followed by 14 days off treatment [14/14 schedule]). Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14) Participants received cobimetinib 80 mg via solution or capsule, once daily for Days 1-14 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14) Participants received cobimetinib 100 mg via solution or capsule, once daily for Days 1-14 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14) Participants received cobimetinib 125 mg via solution or capsule, once daily for Days 1-14 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 2A Cohort 30 - Cobimetinib 100 mg (Expansion) (14/14) Participants received cobimetinib 100 mg via solution or capsule, once daily for Days 1-14 of each 28-day cycle. Treatment was continued until PD or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
Stage 3 Cohort 40 - Cobimetinib+Midazolam+Dextromethorphan Participants received a single dose of midazolam (2 mg of midazolam syrup) and dextromethorphan (30 mg tablet) on Cycle 1 Day 1, in the absence of cobimetinib. After a 2-day washout period, participants received 21 consecutive daily doses of cobimetinib (60-mg) followed by a 7-day washout period.Participants received another single dose of midazolam and dextromethorphan on Cycle 1 Day 15, in the presence of steady-state cobimetinib concentrations. In Cycle 2 and beyond received cobimetinib alone, administered as a 60-mg daily dose for 21 consecutive days in 28-day cycles.
Total Total of all reporting groups

Baseline Measures
    Stage 1 Cohort 01 – Cobimetinib 0.05 mg/kg (21/7)     Stage 1 Cohort 02 – Cobimetinib 0.10 mg/kg (21/7)     Stage 1 Cohort 03 – Cobimetinib 0.20 mg/kg (21/7)     Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7)     Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7)     Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7)     Stage 1 Cohort 07 – Cobimetinib 60 mg (21/7)     Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7)     Stage 2 Cohort 20 – Cobimetinib 60 mg (Expansion) (21/7)     Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14)     Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14)     Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14)     Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14)     Stage 2A Cohort 30 - Cobimetinib 100 mg (Expansion) (14/14)     Stage 3 Cohort 40 - Cobimetinib+Midazolam+Dextromethorphan     Total  
Number of Participants  
[units: participants]
  4     3     3     3     3     6     7     7     21     3     3     8     6     22     20     119  
Age  
[units: years]
Mean (Standard Deviation)
  66.0  (11.52)     60.7  (19.73)     51.3  (6.35)     66.0  (10.82)     60.7  (9.61)     62.0  (12.38)     63.9  (5.87)     54.4  (8.40)     59.7  (13.08)     52.7  (13.20)     49.7  (21.08)     55.1  (13.46)     61.5  (13.61)     61.1  (11.45)     57.1  (15.60)     59.1  (12.8)  
Gender  
[units: participants]
                               
Female     3     0     2     3     1     3     2     3     11     1     3     4     4     10     9     59  
Male     1     3     1     0     2     3     5     4     10     2     0     4     2     12     11     60  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Stage 1 and 1A: Number of Participants With Dose Limiting Toxicities (DLTs)   [ Time Frame: Stage 1 and 1A: Days 1 to 28 of Cycle 1 ]

2.  Primary:   Stage 1: Maximum Tolerated Dose (MTD) of Cobimetinib in 21/7 Schedule   [ Time Frame: Stage 1: Days 1 to 28 of Cycle 1 ]

3.  Primary:   Stage 1A: MTD of Cobimetinib in 14/14 Schedule   [ Time Frame: Stage 1A: Days 1 to 28 of Cycle 1 ]

4.  Primary:   Stage 1: Maximum Observed Concentration (Cmax) of Cobimetinib at Day 1, Cycle 1   [ Time Frame: Stage 1: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 1 and pre-dose on Cycle 1 Day 2 ]

5.  Primary:   Stage 1: Area Under the Plasma Cobimetinib Concentration Curve From Time 0 to 24 Hours (AUC 0-24) Day 1, Cycle 1   [ Time Frame: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2 ]

6.  Primary:   Stage 1: Time to Maximum Concentration (Tmax) of Cobimetinib at Day 1, Cycle 1   [ Time Frame: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 1 and pre-dose on Cycle 1 Day 2 ]

7.  Secondary:   Stage 1: Tmax of Cobimetinib at Steady State   [ Time Frame: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively) ]

8.  Secondary:   Stage 1: AUC 0-24 of Cobimetinib at Steady State   [ Time Frame: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively) ]

9.  Secondary:   Stage 1: AUC 0-24/D of Cobimetinib at Steady State   [ Time Frame: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively) ]

10.  Secondary:   Stage 1: Accumulation Ratio of Cobimetinib at Steady State   [ Time Frame: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 1, Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively) ]

11.  Secondary:   Stage 1: Apparent Clearance of Cobimetinib at Steady State   [ Time Frame: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively) ]

12.  Secondary:   Stage 1: Half-Life (t1/2) of Cobimetinib at Steady State   [ Time Frame: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively) ]

13.  Secondary:   Stage 1: Cmax of Cobimetinib at Steady State   [ Time Frame: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively) ]

14.  Secondary:   Stage 1A: Tmax of Cobimetinib at Cycle 1 Day 1   [ Time Frame: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2 ]

15.  Secondary:   Stage 1A: Cmax of Cobimetinib at Cycle 1 Day 1   [ Time Frame: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2 ]

16.  Secondary:   Stage 1A: AUC 0-24 of Cobimetinib at Cycle 1 Day 1   [ Time Frame: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2 ]

17.  Secondary:   Stage 1A: t1/2 of Cobimetinib at Steady State   [ Time Frame: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively) ]

18.  Secondary:   Stage 1A: Tmax of Cobimetinib at Steady State   [ Time Frame: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively) ]

19.  Secondary:   Stage 1A: Apparent Clearance of Cobimetinib at Steady State   [ Time Frame: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively) ]

20.  Secondary:   Stage 1A: Accumulation Ratio of Cobimetinib at Steady State   [ Time Frame: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively) ]

21.  Secondary:   Stage 1A: AUC 0-24 of Cobimetinib at Steady State   [ Time Frame: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively) ]

22.  Secondary:   Stage 1A: AUC 0-24/D of Cobimetinib at Steady State   [ Time Frame: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively) ]

23.  Secondary:   Stage 1A: Cmax of Cobimetinib at Steady State   [ Time Frame: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively) ]

24.  Secondary:   Stage 2: Cmax of Cobimetinib at Cycle 1 Day 1   [ Time Frame: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2 ]

25.  Secondary:   Stage 2:AUC 0-24 of Cobimetinib at Cycle 1 Day 1   [ Time Frame: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2 ]

26.  Secondary:   Stage 2: Tmax of Cobimetinib at Cycle 1 Day 1   [ Time Frame: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2 ]

27.  Secondary:   Stage 2: Tmax of Cobimetinib at Steady State   [ Time Frame: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28 ]

28.  Secondary:   Stage 2: AUC 0-24 of Cobimetinib at Steady State   [ Time Frame: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28 ]

29.  Secondary:   Stage 2: AUC 0-24/D of Cobimetinib at Steady State   [ Time Frame: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28 ]

30.  Secondary:   Stage 2: Accumulation Ratio of Cobimetinib at Steady State   [ Time Frame: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28 ]

31.  Secondary:   Stage 2: Apparent Clearance of Cobimetinib at Steady State   [ Time Frame: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28 ]

32.  Secondary:   Stage 2:Half-Life of Cobimetinib at Steady State   [ Time Frame: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28 ]

33.  Secondary:   Stage 2A: AUC 0-24/D of Cobimetinib at Steady State   [ Time Frame: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28 ]

34.  Secondary:   Stage 2A: Accumulation Ratio of Cobimetinib at Steady State   [ Time Frame: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28 ]

35.  Secondary:   Stage 2A: Apparent Clearance of Cobimetinib at Steady State   [ Time Frame: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28 ]

36.  Secondary:   Stage 2A: Half-Life of Cobimetinib at Steady State   [ Time Frame: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28 ]

37.  Secondary:   Stage 2A: Tmax of Cobimetinib at Steady State   [ Time Frame: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28 ]

38.  Secondary:   Stage 2A: Cmax of Cobimetinib at Steady State   [ Time Frame: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28 ]

39.  Secondary:   Stage III: Cmax of Dextromethorphan   [ Time Frame: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1 ]

40.  Secondary:   Stage III: AUC 0-24 of Dextromethorphan   [ Time Frame: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1 ]

41.  Secondary:   Stage III: AUC 0-inf of Dextromethorphan   [ Time Frame: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1 ]

42.  Secondary:   Stage III: Cmax of Midazolam   [ Time Frame: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1 ]

43.  Secondary:   Stage III: AUC0-24 of Midazolam   [ Time Frame: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1 ]

44.  Secondary:   Stage III: AUC0-inf of Midazolam   [ Time Frame: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Communications
Organization: Hoffmann-LaRoche
phone: 1-800-821-8590
e-mail: genentech@druginfo.com



Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00467779     History of Changes
Other Study ID Numbers: MEK4592g
GO01329 ( Other Identifier: Hoffmann-La Roche )
XL518-001 ( Other Identifier: Exelixis )
Study First Received: April 18, 2007
Results First Received: June 10, 2016
Last Updated: July 25, 2016
Health Authority: United States: Food and Drug Administration