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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Non-Squamous Non-Small Cell Lung Cancer	Drug: GDC-0941; Drug: bevacizumab; Drug: carboplatin; Drug: cisplatin; Drug: paclitaxel; Drug: pemetrexed	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	65 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase Ib, Open-Label, Dose-Escalation 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
Study Start Date :	October 2009
Actual Primary Completion Date :	March 2015
Actual Study Completion Date :	March 2015

Arms and Interventions

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Arm	Intervention/treatment
Experimental: GDC-0941+Paclitaxel+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	Drug: 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 Drug: carboplatin; Carboplation IV on Day 1 of every 3-week cycle, at a dose to achieve an area under concentration time curve of 6 milligrams per milliliter*minute (mg/mL*min).\n Drug: paclitaxel; Paclitaxel 200 mg/m^2 IV on Day 1 of every 3-week cycle.\n\n
Experimental: GDC-0941+Paclitaxel+Carboplatin+Bevacizumab; Bevacizumab-eligible NSCLC particpants may receive up to 6 cycles of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941 and bevacizumab.	Drug: 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 Drug: bevacizumab; Bevacizumab 15 milligrams per kilograms (mg/kg) intravenously (IV) on Day 1 of every 3-week cycle. Drug: carboplatin; Carboplation IV on Day 1 of every 3-week cycle, at a dose to achieve an area under concentration time curve of 6 milligrams per milliliter*minute (mg/mL*min).\n Drug: paclitaxel; Paclitaxel 200 mg/m^2 IV on Day 1 of every 3-week cycle.\n\n
Experimental: GDC-0941+Pemetrexed+Cisplatin; Bevacizumab-ineligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941.\n	Drug: 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 Drug: bevacizumab; Bevacizumab 15 milligrams per kilograms (mg/kg) intravenously (IV) on Day 1 of every 3-week cycle. Drug: cisplatin; Cisplatin 75 milligrams per square meter (mg/m^2) IV on Day 1 of every 3-week cycle.\n Drug: pemetrexed; Pemetrexed 500 mg/m^2 IV on Day 1 of every 3-week cycle.
Experimental: GDC-0941+Pemetrexed+Cisplatin+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	Drug: 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 Drug: bevacizumab; Bevacizumab 15 milligrams per kilograms (mg/kg) intravenously (IV) on Day 1 of every 3-week cycle. Drug: cisplatin; Cisplatin 75 milligrams per square meter (mg/m^2) IV on Day 1 of every 3-week cycle.\n Drug: pemetrexed; Pemetrexed 500 mg/m^2 IV on Day 1 of every 3-week cycle.

Outcome Measures

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Primary Outcome Measures :

1. Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Days 1 to 22 of Cycle 1 ]
2. Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to approximately 5.5 years ]

Secondary Outcome Measures :

1. 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 ]
2. 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 ]
3. 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". ]
4. 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 ]
5. 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 ]
6. 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) ]
7. 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 ]
8. 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) ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

United States, New York
Buffalo, New York, United States, 14263
France
Villejuif, France, 94805
Netherlands
Groningen, Netherlands, 9700 RB

Sponsors and Collaborators

Genentech, Inc.

Investigators

Study Director:	Clinical Trials	Genentech, Inc.

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Genentech, Inc.
ClinicalTrials.gov Identifier:	NCT00974584 History of Changes
Other Study ID Numbers:	GDC4628g; GO01303 ( Other Identifier: Hoffmann-La Roche )
First Posted:	September 10, 2009
Last Update Posted:	November 2, 2016
Last Verified:	November 2016

Keywords provided by Genentech, Inc.:

NSCLC; PI3K; Avastin

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Paclitaxel; Albumin-Bound Paclitaxel; Cisplatin; Bevacizumab; Carboplatin	Pemetrexed; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors