Back to resultsA 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
Primary Purpose
Non-Squamous Non-Small Cell Lung Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
GDC-0941
bevacizumab
carboplatin
cisplatin
paclitaxel
pemetrexed
Sponsored by
About this trial
This is an interventional treatment trial for Non-Squamous Non-Small Cell Lung Cancer focused on measuring NSCLC, PI3K, Avastin
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
GDC-0941+Paclitaxel+Carboplatin
GDC-0941+Paclitaxel+Carboplatin+Bevacizumab
GDC-0941+Pemetrexed+Cisplatin
GDC-0941+Pemetrexed+Cisplatin+Bevacizumab
Arm Description
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
Bevacizumab-eligible NSCLC particpants may receive up to 6 cycles of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941 and bevacizumab.
Bevacizumab-ineligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941.\n
Bevacizumab-eligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941 and bevacizumab.\n
Outcomes
Primary Outcome Measures
Number of Participants with Dose Limiting Toxicities (DLTs)
Percentage of Participants with Adverse Events (AEs)
Secondary Outcome Measures
Maximum Plasma Concentration of Paclitaxel
Maximum Plasma Concentration of Carboplatin
Maximum Plasma Concentration of Pemetrexed
Maximum Plasma Concentration of Cisplatin
Percentage of Participants with Objective Response (Complete or Partial Response), as Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST)
Duration of Response, as Assessed Using RECIST\n\n\n
Progression-free Survival (PFS), as Assessed Using RECIST\n
Maximum Plasma Concentration of GDC-0941
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00974584
Brief Title
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
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 Type
Interventional
2. Study Status
Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
October 2009 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Squamous Non-Small Cell Lung Cancer
Keywords
NSCLC, PI3K, Avastin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
65 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GDC-0941+Paclitaxel+Carboplatin
Arm Type
Experimental
Arm Description
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
Arm Title
GDC-0941+Paclitaxel+Carboplatin+Bevacizumab
Arm Type
Experimental
Arm Description
Bevacizumab-eligible NSCLC particpants may receive up to 6 cycles of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941 and bevacizumab.
Arm Title
GDC-0941+Pemetrexed+Cisplatin
Arm Type
Experimental
Arm Description
Bevacizumab-ineligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941.\n
Arm Title
GDC-0941+Pemetrexed+Cisplatin+Bevacizumab
Arm Type
Experimental
Arm Description
Bevacizumab-eligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941 and bevacizumab.\n
Intervention Type
Drug
Intervention Name(s)
GDC-0941
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
bevacizumab
Intervention Description
Bevacizumab 15 milligrams per kilograms (mg/kg) intravenously (IV) on Day 1 of every 3-week cycle.
Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Description
Cisplatin 75 milligrams per square meter (mg/m^2) IV on Day 1 of every 3-week cycle.\n
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Intervention Description
Paclitaxel 200 mg/m^2 IV on Day 1 of every 3-week cycle.\n\n
Intervention Type
Drug
Intervention Name(s)
pemetrexed
Intervention Description
Pemetrexed 500 mg/m^2 IV on Day 1 of every 3-week cycle.
Primary Outcome Measure Information:
Title
Number of Participants with Dose Limiting Toxicities (DLTs)
Time Frame
Days 1 to 22 of Cycle 1
Title
Percentage of Participants with Adverse Events (AEs)
Time Frame
Up to approximately 5.5 years
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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".
Title
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
Title
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
Title
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)
Title
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
Title
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
Facility Information:
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
City
Villejuif
ZIP/Postal Code
94805
Country
France
City
Groningen
ZIP/Postal Code
9700 RB
Country
Netherlands
12. IPD Sharing Statement
Learn more about this trial
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
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