Clinical trial NCT00974584: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-Squamous Non-Small Cell Lung Cancer
Keywords: NSCLC
PI3K
Avastin
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2009-09-10
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants with Dose Limiting Toxicities (DLTs)
timeFrame: Days 1 to 22 of Cycle 1
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Up to approximately 5.5 years
Secondary outcomes:
measure: Maximum Plasma Concentration of Paclitaxel
timeFrame: 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
measure: Maximum Plasma Concentration of Carboplatin
timeFrame: Cycle 1 Day 2: Pre-carboplatin infusion, end of Carboplatin infusion, 0.5, 1.5 hours post-carboplatin infusion\n\n
measure: Maximum Plasma Concentration of Pemetrexed
timeFrame: 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".
measure: Maximum Plasma Concentration of Cisplatin
timeFrame: 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
measure: Percentage of Participants with Objective Response (Complete or Partial Response), as Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Screening, Days 15 to 21 of Cycles 2, 4, 6, 9, and every 3 cycles thereafter (up to approximately 5.5 years)\n\n
measure: Duration of Response, as Assessed Using RECIST\n\n\n
timeFrame: Screening, Days 15 to 21 of Cycles 2, 4, 6, 9, and every 3 cycles thereafter (up to approximately 5.5 years)
measure: Progression-free Survival (PFS), as Assessed Using RECIST\n
timeFrame: Screening, Days 15 to 21 of Cycles 2, 4, 6, 9, and every 3 cycles thereafter (up to approximately 5.5 years)\n\n
measure: Maximum Plasma Concentration of GDC-0941
timeFrame: 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)
Other outcomes:
Locations:
city: Buffalo
country: United States
state: New York
city: Villejuif
country: France
city: Groningen
country: Netherlands
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: