Study of Cobimetinib in Participants With Solid Tumors

NCT ID: NCT00467779

Last Updated: 2016-08-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 119 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2014-04-30

Brief Summary

This non-randomized, open-label, study will determine the highest safe dose of cobimetinib, how often it should be taken, how well participants with cancer tolerate cobimetinib and will assess the pharmacokinetic effect of midazolam and dextromethorphan on the study drug.

Conditions

Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stage 1: Cobimetinib Dose Escalation (21/7 Schedule)

Participants will receive cobimetinib (GDC-0973/XL518) at the starting dose of 0.05 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 will continue 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.

Group Type: EXPERIMENTAL

cobimetinib

Intervention Type: DRUG

Repeating oral dose

Stage 1A: Cobimetinib Dose Escalation (14/14 Schedule)

Participants will receive cobimetinib at the starting dose of 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 will continue 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.

Group Type: EXPERIMENTAL

cobimetinib

Intervention Type: DRUG

Repeating oral dose

Stage 2: Cobimetinib Expansion (21/7 Schedule)

Participants will receive cobimetinib at the maximum tolerated dose (MTD) established in Stage 1, 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 will continue 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.

Group Type: EXPERIMENTAL

cobimetinib

Intervention Type: DRUG

Repeating oral dose

Stage 2 A: Cobimetinib Expansion (14/14 Schedule)

Participants will receive cobimetinib at the MTD established in Stage 1A, 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 will continue 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.

Group Type: EXPERIMENTAL

cobimetinib

Intervention Type: DRUG

Repeating oral dose

Stage 3: Cobimetinib+Midazolam+Dextromethorphan

Participants will receive 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 will receive 21 consecutive daily doses of cobimetinib (60-mg) followed by a 7-day washout period. Participants will receive 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 participants will receive cobimetinib alone, administered as a 60-mg daily dose for 21 consecutive days in 28-day cycles (21/7 schedule).

Group Type: EXPERIMENTAL

cobimetinib

Intervention Type: DRUG

Repeating oral dose

dextromethorphan

Intervention Type: DRUG

In Stage III only: single dose of dextromethorphan

midazolam

Intervention Type: DRUG

In Stage III only: single dose of midazolam

Interventions

cobimetinib

Repeating oral dose

Intervention Type: DRUG

dextromethorphan

In Stage III only: single dose of dextromethorphan

Intervention Type: DRUG

midazolam

In Stage III only: single dose of midazolam

Intervention Type: DRUG

Other Intervention Names

GDC-0973/XL518

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed solid tumor that is metastatic or unresectable, and for which standard curative or palliative measures do not exist or are no longer effective, and there are no known therapies to prolong survival
• Disease that is measurable according to Response Evaluation Criteria in Solid Tumors (RECIST)
• Adequate organ and marrow function
• Sexually active participants must use medically acceptable methods of contraception during the course of the study and at least 11 days after the last dose of study treatment
• Female participants of childbearing potential must have a negative serum pregnancy test at screening
• No other history of/or ongoing malignancy that would potentially interfere with the interpretation of the pharmacodynamic or efficacy assays

Exclusion Criteria

• Anticancer treatment (e.g., chemotherapy, radiotherapy, cytokines, or hormones) within 28 days (6 weeks for nitrosoureas or mitomycin C, or 14 days for hormonal therapy or kinase inhibitors) before the first dose of study drug
• The participant has not recovered to Grade </=1 from adverse events (AEs) or to within 10% of baseline values due to investigational or other agents administered more than 28 days prior to study enrollment
• The participant has received another investigational agent within 28 days of the first dose of study drug
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, diabetes, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
• The participant is pregnant or breastfeeding
• The participant is known to be positive for the human immunodeficiency virus (HIV)
• Allergy or hypersensitivity to components of the cobimetinib formulation

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

Los Angeles, California, United States

Stanford, California, United States

Detroit, Michigan, United States

Buffalo, New York, United States

Countries

United States

Other Identifiers

GO01329

Identifier Type: OTHER

Identifier Source: secondary_id

XL518-001

Identifier Type: OTHER

Identifier Source: secondary_id

MEK4592g

Identifier Type: -

Identifier Source: org_study_id