A Study of the Safety, Tolerability, and Effects of Cobimetinib and GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors

• Status: Completed
• Trial end date: 2016-12-05
• Target enrollment: 0
• Participant gender: All

Summary

This is a two-stage dose-escalation study to assess the safety, tolerability and effects of oral dosing of cobimetinib and GDC-0994 administered in combination in patients with histologically confirmed, locally advanced, or metastatic solid tumors for which standard therapies either do not exist or have proven ineffective or intolerable.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Genentech, Inc.
• Treatments: Ravoxertinib

Criteria

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Histologically or cytologically documented, locally advanced or metastatic solid tumors for which standard therapy either does not exist or has proven ineffective or intolerable

• Evaluable disease or disease measurable

• Life expectancy > or = 12 weeks

• Adequate hematologic and end organ function

• For female patients of childbearing potential and male patients with partners of childbearing potential, use of an effective form of contraception with continued use for study duration and up to 3 months or more following discontinuation of treatment drug

• Fluorodeoxyglucose positron emission tomography (FDG-PET) avid disease on baseline scan

For enrollment in part 2, patients must meet all of the following:

• Measurable disease

• No more than four prior systemic therapies for locally advanced or metastatic cancer

Exclusion Criteria:

• History of prior significant toxicity from another MEK inhibitor or ERK inhibitor requiring discontinuation of treatment

• Evidence of visible retinal pathology as assessed by ophthalmologic examination that is considered a risk factor for retinal vein thrombosis

• History of glaucoma

• Intraocular pressure > 21 mmHg as measured by tonometry

• Predisposing factors to retinal vein occlusion (RVO)

• History of RVO, neurosensory retinal detachment, or neovascular macular degeneration

• Allergy or hypersensitivity to components of the cobimetinib or GDC-0994 formulation

• Palliative radiotherapy within 2 weeks prior to first dose of study-drug treatment in Cycle 1

• Experimental therapy within 4 weeks prior to first dose of study-drug treatment in Cycle 1

• Major surgical procedure or significant traumatic injury within 4 weeks prior to the first dose of study-drug treatment in Cycle 1, or anticipation of the need for major surgery during the course of study treatment

• Anti-cancer therapy within 28 days prior to the first dose of study-drug treatment in Cycle 1

• Current severe, uncontrolled systemic disease

• History of clinically significant cardiac dysfunction

• History of symptomatic congestive heart failure or serious cardiac arrhythmia requiring treatment

• History of myocardial infarction within 6 months prior to the first dose of study-drug treatment in Cycle 1

• History of congenital long QT syndrome or QTc > 470 msec

• LVEF

• History of malabsorption or other condition that would interfere with enteral absorption

• Clinically significant history of liver disease, current alcohol abuse, or current known active infection with HIV, hepatitis B virus, or hepatitis C virus

• Any condition requiring warfarin or thrombolytic anticoagulants

• Active autoimmune disease

• Uncontrolled ascites requiring weekly large volume paracentesis for 3 consecutive weeks prior to enrollment

• Pregnancy, lactation, or breastfeeding

• Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms

• No other history of or ongoing malignancy that would potentially interfere with the interpretation of the Pharmacodynamic (PD) or efficacy assays