A Study of the Safety and Pharmacology Of PI3-Kinase Inhibitor GDC-0941 In Combination With Either Paclitaxel And Carboplatin (With or Without Bevacizumab) or Pemetrexed, Cisplatin, And Bevacizumab in Patients With Advanced Non-Small Cell Lung Cancer

Genentech, Inc.65 enrolled

Overview

This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of oral (PO) GDC-0941 administered with one of three planned regimens: Arm A: paclitaxel and carboplatin in bevacizumab-ineligible NSCLC patients, Arm B: paclitaxel, carboplatin, and bevacizumab in bevacizumab-eligible NSCLC patients and Arm C: pemetrexed, cisplatin, and bevacizumab in bevacizumab-eligible, non-squamous NSCLC patients.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Non-Squamous Non-Small Cell Lung Cancer

Interventions

GDC-0941

The GDC-0941 at a starting dose of 60 milligrams (mg) will be administered once daily orally for 14 consecutive days (Days 1 to 14) in 3-week cycles except for the first cycle that has Day 1 of single-agent GDC-0941 preceding Day 2 with combination chemotherapy.\\n\\n\\n\\n\\n\\n

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically or cytologically documented NSCLC with advanced disease (Stage IIIb not eligible for chemoradiotherapy or Stage IV or recurrent disease) * Adequate organ function as assessed by laboratory tests * Evaluable disease or disease measurable per Response Evaluation Criteria in Solid Tumors (RECIST) Exclusion Criteria: * More than one anti-cancer regimen (chemotherapy or radiotherapy) for advanced NSCLC prior to initiation of study treatment * Any adjuvant or neoadjuvant anti-cancer therapy within a specified timeframe prior to first study treatment * History of Grade \>= 3 fasting hyperglycemia or diabetes requiring regular medication * Active autoimmune disease, active infection requiring IV antibiotics, or other current uncontrolled illness * History of clinically significant cardiac or pulmonary dysfunction * History of malabsorption syndrome or other condition that would interfere with enteral absorption * Clinically significant history of liver disease * Any condition requiring full-dose anticoagulants, such as warfarin, heparin, or thrombolytic agents * Known brain metastases that are untreated, symptomatic, or require therapy * Pregnancy, lactation, or breastfeeding

Locations (3)

Unnamed facility

Buffalo, New York, United States

Unnamed facility

Villejuif, France

Unnamed facility

Groningen, Netherlands

Outcomes

Primary Outcomes

Number of Participants with Dose Limiting Toxicities (DLTs)

Time frame: Days 1 to 22 of Cycle 1

Percentage of Participants with Adverse Events (AEs)

Time frame: Up to approximately 5.5 years

Secondary Outcomes

Maximum Plasma Concentration of Paclitaxel

Time frame: Cycle 1 Day 2: Pre-paclitaxel infusion, end of paclitaxel infusion, 0.5, 1 and 2 hours post-paclitaxel infusion; Cycle 1 Day 3: Pre-GDC-0941 dose, 24 hours post-paclitaxel Day 2 infusion

Maximum Plasma Concentration of Carboplatin

Time frame: Cycle 1 Day 2: Pre-carboplatin infusion, end of Carboplatin infusion, 0.5, 1.5 hours post-carboplatin infusion\n\n

Maximum Plasma Concentration of Pemetrexed

Time frame: Cycle 1 Day 2: Pre-pemetrexed infusion, end of pemetrexed infusion, 1, 3 hours post-pemetrexed infusion; Cycle 1 Day 3: Pre-GDC-0941 dose, 24 hours post-pemetrexed Day 2 infusion\n\nd be "Yes".

Maximum Plasma Concentration of Cisplatin

Time frame: Cycle 1 Day 2: Pre-cisplatin infusion, end of cisplatin infusion, 3 hours post-cisplatin infusion; Cycle 1 Day 3: Pre-GDC-0941 dose, 24 hours post-pemetrexed Day 2 infusion\n\n

Percentage of Participants with Objective Response (Complete or Partial Response), as Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST)

Time frame: Screening, Days 15 to 21 of Cycles 2, 4, 6, 9, and every 3 cycles thereafter (up to approximately 5.5 years)\n\n

Duration of Response, as Assessed Using RECIST\n\n\n

Time frame: Screening, Days 15 to 21 of Cycles 2, 4, 6, 9, and every 3 cycles thereafter (up to approximately 5.5 years)

Progression-free Survival (PFS), as Assessed Using RECIST\n

Time frame: Screening, Days 15 to 21 of Cycles 2, 4, 6, 9, and every 3 cycles thereafter (up to approximately 5.5 years)\n\n

Maximum Plasma Concentration of GDC-0941

Time frame: Cycle 1 Days 1 and 2: Pre-GDC-0941 dose, 1, 2, 3 and 4 hours post-GDC-0941 dose; Cycle 1 Days 3 and 9: Pre-GDC-0941 dose; 30 days after last dose of study treatment (up to approximately 5.5 years)