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 - Full Text View

Purpose

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	Intervention	Phase
Non-Squamous Non-Small Cell Lung Cancer	Drug: GDC-0941 Drug: bevacizumab Drug: carboplatin Drug: cisplatin Drug: paclitaxel Drug: pemetrexed	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: lung cancer

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Cisplatin Paclitaxel Carboplatin Pemetrexed Pemetrexed disodium Bevacizumab

U.S. FDA Resources

Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:

Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Days 1 to 22 of Cycle 1 ] [ Designated as safety issue: No ]
Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to approximately 5.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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". ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]


Enrollment:	65
Study Start Date:	October 2009
Study Completion Date:	March 2015
Primary Completion Date:	March 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 milliliterminute (mg/mLmin).\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 milliliterminute (mg/mLmin).\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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00974584

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


Responsible Party:	Genentech, Inc.
ClinicalTrials.gov Identifier:	NCT00974584 History of Changes
Other Study ID Numbers:	GDC4628g GO01303
Study First Received:	September 8, 2009
Last Updated:	September 1, 2016
Health Authority:	United States: Food and Drug Administration

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 Pemetrexed	Carboplatin 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

ClinicalTrials.gov processed this record on September 26, 2016