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

NCT00974584 | Completed Phase 1

• 2 other identifiers: GDC4628gGO01303
• Study Type: interventional
• Target: 65
• Locations: 3 countries
• Sites: 3

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.

Conditions

Non-Squamous Non-Small Cell Lung Cancer

Keywords

NSCLC; PI3K; Avastin

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• 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

Study Arms (4)

GDC-0941+Paclitaxel+Carboplatin

EXPERIMENTAL

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; Drug: carboplatin; Drug: paclitaxel

GDC-0941+Paclitaxel+Carboplatin+Bevacizumab

EXPERIMENTAL

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; Drug: bevacizumab; Drug: carboplatin; Drug: paclitaxel

GDC-0941+Pemetrexed+Cisplatin

EXPERIMENTAL

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; Drug: bevacizumab; Drug: cisplatin; Drug: pemetrexed

GDC-0941+Pemetrexed+Cisplatin+Bevacizumab

EXPERIMENTAL

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; Drug: bevacizumab; Drug: cisplatin; Drug: pemetrexed

Interventions

GDC-0941 DRUG

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

GDC-0941+Paclitaxel+Carboplatin; GDC-0941+Paclitaxel+Carboplatin+Bevacizumab; GDC-0941+Pemetrexed+Cisplatin; GDC-0941+Pemetrexed+Cisplatin+Bevacizumab

bevacizumab DRUG

Bevacizumab 15 milligrams per kilograms (mg/kg) intravenously (IV) on Day 1 of every 3-week cycle.

GDC-0941+Paclitaxel+Carboplatin+Bevacizumab; GDC-0941+Pemetrexed+Cisplatin; GDC-0941+Pemetrexed+Cisplatin+Bevacizumab

carboplatin DRUG

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

GDC-0941+Paclitaxel+Carboplatin; GDC-0941+Paclitaxel+Carboplatin+Bevacizumab

cisplatin DRUG

Cisplatin 75 milligrams per square meter (mg/m\^2) IV on Day 1 of every 3-week cycle.\\n

GDC-0941+Pemetrexed+Cisplatin; GDC-0941+Pemetrexed+Cisplatin+Bevacizumab

paclitaxel DRUG

Paclitaxel 200 mg/m\^2 IV on Day 1 of every 3-week cycle.\\n\\n

GDC-0941+Paclitaxel+Carboplatin; GDC-0941+Paclitaxel+Carboplatin+Bevacizumab

pemetrexed DRUG

Pemetrexed 500 mg/m\^2 IV on Day 1 of every 3-week cycle.

GDC-0941+Pemetrexed+Cisplatin; GDC-0941+Pemetrexed+Cisplatin+Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (3)

Unknown Facility

Buffalo, New York, 14263, United States

Location

Unknown Facility

Villejuif, 94805, France

Location

Unknown Facility

Groningen, 9700 RB, Netherlands

Location

MeSH Terms

Interventions

2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine; Bevacizumab; Carboplatin; Cisplatin; Paclitaxel; Pemetrexed

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2009
• First Posted: September 10, 2009
• Study Start: October 1, 2009
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

FR (1); US (1); NL (1)