Non-Squamous Non-Small Cell Lung Cancer
Conditions
Keywords
NSCLC, PI3K, Avastin
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.
Interventions
DRUGGDC-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
DRUGbevacizumab
Bevacizumab 15 milligrams per kilograms (mg/kg) intravenously (IV) on Day 1 of every 3-week cycle.
DRUGcarboplatin
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
DRUGcisplatin
Cisplatin 75 milligrams per square meter (mg/m\^2) IV on Day 1 of every 3-week cycle.\\n
DRUGpaclitaxel
Paclitaxel 200 mg/m\^2 IV on Day 1 of every 3-week cycle.\\n\\n
DRUGpemetrexed
Pemetrexed 500 mg/m\^2 IV on Day 1 of every 3-week cycle.
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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) |
| 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) |
| 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 |
Countries
France, Netherlands, United States
Outcome results
None listed