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

Phase 1

Completed

• Conditions: Non-Squamous Non-Small Cell Lung Cancer
• Interventions: Drug: GDC-0941; Drug: carboplatin; Drug: bevacizumab; Drug: paclitaxel; Drug: cisplatin; Drug: pemetrexed

• Registration Number: NCT00974584
• Lead Sponsor: Genentech, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-09-08
• Study First Submitted QC: 2009-09-08
• Study First Posted: 2009-09-10
• Study Start: 2009-10
• Primary Completion: 2015-03
• Study Completion: 2015-03
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-01
• Last Update Posted: 2016-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 65

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GDC-0941+Paclitaxel+Carboplatin	GDC-0941	Bevacizumab-ineligible non-small cell lung cancer (NSCLC) participants may receive up to 6 cycles (21-day cycle) of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941
GDC-0941+Paclitaxel+Carboplatin	carboplatin	Bevacizumab-ineligible non-small cell lung cancer (NSCLC) participants may receive up to 6 cycles (21-day cycle) of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941
GDC-0941+Paclitaxel+Carboplatin	paclitaxel	Bevacizumab-ineligible non-small cell lung cancer (NSCLC) participants may receive up to 6 cycles (21-day cycle) of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941
GDC-0941+Paclitaxel+Carboplatin+Bevacizumab	GDC-0941	Bevacizumab-eligible NSCLC particpants may receive up to 6 cycles of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941 and bevacizumab.
GDC-0941+Paclitaxel+Carboplatin+Bevacizumab	bevacizumab	Bevacizumab-eligible NSCLC particpants may receive up to 6 cycles of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941 and bevacizumab.
GDC-0941+Paclitaxel+Carboplatin+Bevacizumab	carboplatin	Bevacizumab-eligible NSCLC particpants may receive up to 6 cycles of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941 and bevacizumab.
GDC-0941+Paclitaxel+Carboplatin+Bevacizumab	paclitaxel	Bevacizumab-eligible NSCLC particpants may receive up to 6 cycles of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941 and bevacizumab.
GDC-0941+Pemetrexed+Cisplatin	GDC-0941	Bevacizumab-ineligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941.\\n
GDC-0941+Pemetrexed+Cisplatin	bevacizumab	Bevacizumab-ineligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941.\\n
GDC-0941+Pemetrexed+Cisplatin	pemetrexed	Bevacizumab-ineligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941.\\n
GDC-0941+Pemetrexed+Cisplatin+Bevacizumab	GDC-0941	Bevacizumab-eligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941 and bevacizumab.\\n
GDC-0941+Pemetrexed+Cisplatin+Bevacizumab	pemetrexed	Bevacizumab-eligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941 and bevacizumab.\\n
GDC-0941+Pemetrexed+Cisplatin	cisplatin	Bevacizumab-ineligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941.\\n
GDC-0941+Pemetrexed+Cisplatin+Bevacizumab	bevacizumab	Bevacizumab-eligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941 and bevacizumab.\\n
GDC-0941+Pemetrexed+Cisplatin+Bevacizumab	cisplatin	Bevacizumab-eligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941 and bevacizumab.\\n

Primary Outcome Measures

Name	Time	Method
Number of Participants with Dose Limiting Toxicities (DLTs)	Days 1 to 22 of Cycle 1
Percentage of Participants with Adverse Events (AEs)	Up to approximately 5.5 years

Secondary Outcome Measures

Name	Time	Method
Maximum Plasma Concentration of Paclitaxel	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	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	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	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)	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	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	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	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)