Safety, Tolerability and Pharmacokinetics of Cobimetinib in Combination With Pictilisib in Patients With Locally Advanced or Metastatic Solid Tumors

• Status: Terminated
• Trial end date: 2014-03-01
• Target enrollment: 0
• Participant gender: All

Summary

This is an open-label, multicenter, Phase Ib dose-escalation study designed to assess the safety, tolerability and pharmacokinetics of oral dosing of cobimetinib and pictilisib administered in combination in patients with locally advanced or metastatic solid tumors.

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

Details

• Lead Sponsor: Genentech, Inc.

Criteria

Inclusion Criteria:

• 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 per Response Evaluation Criteria in Solid Tumors (RECIST)

• Life expectancy greater than or equal to (>=) 12 weeks

• Adequate hematologic and end organ function

• Agreement to use an effective form of contraception for the duration of the study

Exclusion Criteria:

• History of prior significant toxicity from another mitogen-activated protein kinase (MEK) pathway inhibitor requiring discontinuation of treatment

• History of prior significant toxicity from another phosphoinositide 3-kinase (PI3K) pathway inhibitor requiring discontinuation of treatment

• Allergy or hypersensitivity to components of the cobimetinib or pictilisib formulations

• 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 first dose of study drug treatment in Cycle 1, or anticipation of the need for major surgery during the course of study treatment

• Prior anti-cancer therapy within 28 days before the first dose of study drug treatment in Cycle 1

• History of diabetes requiring daily medication, or history of Grade >= 3 fasting hyperglycemia

• Current severe, uncontrolled systemic disease

• History of clinically significant cardiac or pulmonary dysfunction

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

• Clinically significant history of liver disease (including cirrhosis), current alcohol abuse, or current known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus

• Any condition requiring anticoagulants, such as warfarin, heparin, or thrombolytics

• 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 or efficacy assays