Clinical trial NCT00996892: Safety, Tolerability and Pharmacokinetics of Cobimetinib in Combination With Pictilisib in Patients With Locally Advanced or Metastatic Solid Tumors
Official title: A Phase Ib, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability and Pharmacokinetics of GDC-0973 in Combination With GDC-0941 When Administered in Patients With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: GDC0941
GDC0973
MEK
MEK Inhibitor
PI3K
PI3K Inhibitor
PI3 Kinase
PI3 Kinase Inhibitor
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2009-10-16
Enrollment: 178
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B
timeFrame: Cohorts 1-3: Day 1 to Day 35, All other cohorts: Day 1 to Day 28
measure: Maximum Tolerated Combination Doses of Cobimetinib and Pictilisib During Dose-Escalation Stages 1, 1A and 1B
timeFrame: Cohorts 1-3: Day 1 to Day 35, All other cohorts: Day 1 to Day 28
measure: Time of Maximum Concentration (Tmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3
timeFrame: 0-4 hours pre-cobimetinib (Pr-C) dose, 0.5, 2, 4, 6 hours post-cobimetinib (Po-C) dose on Day 3, Day 4
measure: Maximum Plasma Concentration (Cmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3
timeFrame: 0-4 hours Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Day 3, Day 4
measure: Area Under the Concentration-Time Curve From Time 0 to 24 Hours Post-Dose (AUC0-24) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3
timeFrame: 0-4 hours Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Day 3, Day 4
measure: Tmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3
timeFrame: 0-4 hours pre-pictilisib (Pr-P) dose, 0.5, 2, 4, 6 hours post-pictilisib (Po-P) dose on Day 1, Day 2, 0-4 hours Pr-C dose on Day 3
measure: Cmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3
timeFrame: 0-4 hours Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Day 1, Day 2, 0-4 hours Pr-C dose on Day 3
measure: AUC0-24 of Pictilisib on Day 1 - Stage 1, Cohorts 1-3
timeFrame: 0-4 hours Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Day 1, Day 2, 0-4 hours Pr-C dose on Day 3
Secondary outcomes:
measure: Tmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 8, Cycle 1 Days 9, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2, 8, 14
measure: Cmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 8, Cycle 1 Days 9, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2, 8, 14
measure: AUC0-24 of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 8, Cycle 1 Days 9; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2
measure: Tmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
measure: Cmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
measure: AUC0-24 of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 28, Cycle 1 Day 29; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22
measure: Terminal Half-life (t1/2) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
measure: Apparent Clearance (CL/F) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
measure: Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Days 8 and 28, Cycle 1 Days 9, 29; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Days 1 and 21, Cycle 1 Days 2, 22
measure: Tmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 8, Cycle 1 Day 9, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2, 8, 14
measure: Cmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 8, Cycle 1 Day 9, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2, 8, 14
measure: AUC0-24 of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 8, Cycle 1 Day 9; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2
measure: Tmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
measure: Cmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
measure: AUC0-24 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 28, Cycle 1 Day 29; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22
measure: t1/2 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
measure: CL/F of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
measure: Accumulation Ratio of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
timeFrame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Days 8 and 28, Cycle 1 Days 9, 29; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Days 1 and 21, Cycle 1 Day 2, 22
measure: Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17
measure: Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17
measure: AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2
measure: Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19
measure: t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Days 1 and 18, Cycle 1 Days 2, 19
measure: Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17
measure: Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17
measure: AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2
measure: Tmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: Cmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19
measure: t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: CL/F of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Days 1 and 18, Cycle 1 Days 2, 19
measure: Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2
measure: Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2
measure: AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2
measure: Tmax of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22
measure: Cmax of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22
measure: AUC0-24 of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22
measure: CL/F of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22
measure: Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Days 1 and 21, Cycle 1 Days 2 and 22
measure: Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2
measure: Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2
measure: AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2
measure: Tmax of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22
measure: Cmax of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22
measure: AUC0-24 of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22
measure: CL/F of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22
measure: Accumulation Ratio of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Days 1 and 21, Cycle 1 Days 2 and 22
measure: Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 14
measure: Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 14
measure: AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 2 All Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2
measure: Tmax of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
measure: Cmax of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
measure: AUC0-24 of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22
measure: t1/2 of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22
measure: CL/F of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
measure: Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Days 1 and 21, Cycle 1 Days 2 and 22
measure: Tmax of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 14
measure: Cmax of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 14
measure: AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2
measure: Tmax of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
measure: Cmax of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
measure: AUC0-24 of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22
measure: t1/2 of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
measure: CL/F of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
measure: Accumulation Ratio of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Days 1 and 21, Cycle 1 Days 2 and 22
measure: Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17
measure: Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17
measure: AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2
measure: Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: Tmax of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17
measure: Cmax of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17
measure: AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2
measure: Tmax of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: Cmax of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: CL/F of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
timeFrame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
measure: Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B
timeFrame: Up to 30 days after last dose (last dose = up to Cycle 15, cycle length = 28 days)
measure: Duration of Objective Response - Dose Escalation Stages 1, 1A and 1B
timeFrame: Up to 30 days after last dose (last dose = up to Cycle 15, cycle length = 28 days)
measure: Progression-Free Survival (PFS) - Dose Escalation Stages 1, 1A and 1B
timeFrame: Up to 30 days after last dose (last dose = up to Cycle 15, cycle length = 28 days)
Other outcomes:
Locations:
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Oklahoma City
country: United States
state: Oklahoma
city: Nashville
country: United States
state: Tennessee
Study officials:
affiliation: Genentech, Inc.
name: Iris Chan, M.D., Ph.D.
role: STUDY_DIRECTOR
References: