A Phase II, Double-Blind, Placebo-Controlled, Randomized Study Evaluating the Safety and Efficacy of Carboplatin/Paclitaxel and Carboplatin/Paclitaxel/Bevacizumab With and Without GDC-0941 in Patients With Previously Untreated Advanced or Recurrent Non-small Cell Lung Cancer
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Genentech, Inc.
- Enrollment
- 501
- Locations
- 120
- Primary Endpoint
- Progression-free Survival (PFS)
Study Overview
Brief Summary
This multicenter, randomized, double-blind, placebo-controlled trial will evaluate the efficacy and safety of carboplatin/paclitaxel and carboplatin/paclitaxel/bevacizumab with and without pictilisib in particpants with previously untreated advanced or recurrent non-small cell lung cancer (NSCLC). Particpants will be randomized to receive 4 cycles of carboplatin (C)/paclitaxel (P) and either pictilisib or placebo, with (participants with non-squamous NSCLC) or without (participants with squamous NSCLC) bevacizumab (B). Anticipated time on study treatment is until disease progression or intolerable toxicity occurs. Participants in placebo arms with disease progression may cross over to open-label active pictilisib.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically documented advanced (Stage IV) or recurrent squamous (Arms A and B) or non-squamous (Arms C, D, E, and F) non-small cell lung cancer (NSCLC)
- •Consent to the collection of an archival formalin-fixed paraffin-embedded (FFPE) block or freshly cut unstained tumor slides from archival tumor tissue or a newly collected tumor sample
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Disease that is measurable per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
- •Adequate hematologic and end organ function
- •Use of two effective forms of contraception
Exclusion Criteria
- •NSCLC with documented epidermal growth factor receptor (EGFR) mutation associated with response to EGFR inhibitors or documented fusion gene involving anaplastic lymphoma kinase (ALK) gene
- •Prior therapy (including chemotherapy, antibody therapy, tyrosine kinase inhibitors, radiotherapy, immunotherapy, hormonal therapy, or investigational therapy) before Day 1 of Cycle 1 for the treatment of advanced (Stage IV) or recurrent NSCLC
- •Known central nervous system (CNS) disease except for treated brain metastases
- •Type I diabetes
- •Type II diabetes requiring chronic therapy with insulin
- •Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk for treatment complications
- •Medical conditions that would contraindicate bevacizumab therapy in non-squamous NSCLC (Arms C, D, E, and F)
Arms & Interventions
Arm A: 340 mg pictilisib + CP
Participants with advanced (Stage IV) or recurrent squamous NSCLC will be administered 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P).
Intervention: pictilisib (Drug)
Arm A: 340 mg pictilisib + CP
Participants with advanced (Stage IV) or recurrent squamous NSCLC will be administered 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P).
Intervention: carboplatin (Drug)
Arm A: 340 mg pictilisib + CP
Participants with advanced (Stage IV) or recurrent squamous NSCLC will be administered 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P).
Intervention: paclitaxel (Drug)
Arm B: Placebo + CP
Participants with advanced (Stage IV) or recurrent squamous NSCLC will be administered placebo corresponding to 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P). Participants with investigator assessed radiographic progression of NSCLC per RECIST 1.1 will be allowed to cross over to Arm A during the first 4 cycles with carboplatin + paclitaxel or after chemotherapy has been completed (Cycle >/= 5).
Intervention: Placebo (Drug)
Arm B: Placebo + CP
Participants with advanced (Stage IV) or recurrent squamous NSCLC will be administered placebo corresponding to 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P). Participants with investigator assessed radiographic progression of NSCLC per RECIST 1.1 will be allowed to cross over to Arm A during the first 4 cycles with carboplatin + paclitaxel or after chemotherapy has been completed (Cycle >/= 5).
Intervention: carboplatin (Drug)
Arm B: Placebo + CP
Participants with advanced (Stage IV) or recurrent squamous NSCLC will be administered placebo corresponding to 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P). Participants with investigator assessed radiographic progression of NSCLC per RECIST 1.1 will be allowed to cross over to Arm A during the first 4 cycles with carboplatin + paclitaxel or after chemotherapy has been completed (Cycle >/= 5).
Intervention: paclitaxel (Drug)
Arm C: 340 mg pictilisib + CPB
Participants with advanced (Stage IV) or recurrent non-squamous NSCLC will be administered 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P) plus bevacizumab (B).
Intervention: pictilisib (Drug)
Arm C: 340 mg pictilisib + CPB
Participants with advanced (Stage IV) or recurrent non-squamous NSCLC will be administered 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P) plus bevacizumab (B).
Intervention: bevacizumab (Drug)
Arm C: 340 mg pictilisib + CPB
Participants with advanced (Stage IV) or recurrent non-squamous NSCLC will be administered 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P) plus bevacizumab (B).
Intervention: carboplatin (Drug)
Arm C: 340 mg pictilisib + CPB
Participants with advanced (Stage IV) or recurrent non-squamous NSCLC will be administered 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P) plus bevacizumab (B).
Intervention: paclitaxel (Drug)
Arm D: Placebo + CPB
Participants with advanced (Stage IV) or recurrent non-squamous NSCLC will be administered placebo corresponding to 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P). Participants with investigator assessed radiographic progression of NSCLC per RECIST 1.1 will be allowed to cross over to Arm C during the first 4 cycles with carboplatin + paclitaxel + bevacizumab or after chemotherapy has been completed (Cycle >/= 5).
Intervention: Placebo (Drug)
Arm D: Placebo + CPB
Participants with advanced (Stage IV) or recurrent non-squamous NSCLC will be administered placebo corresponding to 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P). Participants with investigator assessed radiographic progression of NSCLC per RECIST 1.1 will be allowed to cross over to Arm C during the first 4 cycles with carboplatin + paclitaxel + bevacizumab or after chemotherapy has been completed (Cycle >/= 5).
Intervention: bevacizumab (Drug)
Arm D: Placebo + CPB
Participants with advanced (Stage IV) or recurrent non-squamous NSCLC will be administered placebo corresponding to 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P). Participants with investigator assessed radiographic progression of NSCLC per RECIST 1.1 will be allowed to cross over to Arm C during the first 4 cycles with carboplatin + paclitaxel + bevacizumab or after chemotherapy has been completed (Cycle >/= 5).
Intervention: carboplatin (Drug)
Arm D: Placebo + CPB
Participants with advanced (Stage IV) or recurrent non-squamous NSCLC will be administered placebo corresponding to 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P). Participants with investigator assessed radiographic progression of NSCLC per RECIST 1.1 will be allowed to cross over to Arm C during the first 4 cycles with carboplatin + paclitaxel + bevacizumab or after chemotherapy has been completed (Cycle >/= 5).
Intervention: paclitaxel (Drug)
Arm E: 260 mg pictilisib + CPB
Participants with advanced (Stage IV) or recurrent non-squamous NSCLC will be administered 260 mg pictilisib plus carboplatin (C) plus paclitaxel (P) plus bevacizumab (B).
Intervention: pictilisib (Drug)
Arm E: 260 mg pictilisib + CPB
Participants with advanced (Stage IV) or recurrent non-squamous NSCLC will be administered 260 mg pictilisib plus carboplatin (C) plus paclitaxel (P) plus bevacizumab (B).
Intervention: bevacizumab (Drug)
Arm E: 260 mg pictilisib + CPB
Participants with advanced (Stage IV) or recurrent non-squamous NSCLC will be administered 260 mg pictilisib plus carboplatin (C) plus paclitaxel (P) plus bevacizumab (B).
Intervention: carboplatin (Drug)
Arm E: 260 mg pictilisib + CPB
Participants with advanced (Stage IV) or recurrent non-squamous NSCLC will be administered 260 mg pictilisib plus carboplatin (C) plus paclitaxel (P) plus bevacizumab (B).
Intervention: paclitaxel (Drug)
Arm F: Placebo + CPB
Participants with advanced (Stage IV) or recurrent non-squamous NSCLC will be administered placebo corresponding to 260 mg pictilisib plus carboplatin (C) plus paclitaxel (P). Participants with investigator assessed radiographic progression of NSCLC per RECIST 1.1 will be allowed to cross over to Arm E during the first 4 cycles with carboplatin + paclitaxel + bevacizumab or after chemotherapy has been completed (Cycle >/= 5).
Intervention: Placebo (Drug)
Arm F: Placebo + CPB
Participants with advanced (Stage IV) or recurrent non-squamous NSCLC will be administered placebo corresponding to 260 mg pictilisib plus carboplatin (C) plus paclitaxel (P). Participants with investigator assessed radiographic progression of NSCLC per RECIST 1.1 will be allowed to cross over to Arm E during the first 4 cycles with carboplatin + paclitaxel + bevacizumab or after chemotherapy has been completed (Cycle >/= 5).
Intervention: bevacizumab (Drug)
Arm F: Placebo + CPB
Participants with advanced (Stage IV) or recurrent non-squamous NSCLC will be administered placebo corresponding to 260 mg pictilisib plus carboplatin (C) plus paclitaxel (P). Participants with investigator assessed radiographic progression of NSCLC per RECIST 1.1 will be allowed to cross over to Arm E during the first 4 cycles with carboplatin + paclitaxel + bevacizumab or after chemotherapy has been completed (Cycle >/= 5).
Intervention: carboplatin (Drug)
Arm F: Placebo + CPB
Participants with advanced (Stage IV) or recurrent non-squamous NSCLC will be administered placebo corresponding to 260 mg pictilisib plus carboplatin (C) plus paclitaxel (P). Participants with investigator assessed radiographic progression of NSCLC per RECIST 1.1 will be allowed to cross over to Arm E during the first 4 cycles with carboplatin + paclitaxel + bevacizumab or after chemotherapy has been completed (Cycle >/= 5).
Intervention: paclitaxel (Drug)
Outcomes
Primary Outcomes
Progression-free Survival (PFS)
Time Frame: Up to approximately 2.5 years
PFS in Participants with Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) Amplification
Time Frame: Up to approximately 2.5 years
PFS in Participants with Phosphatase and Tensin Homolog (PTEN) Loss/Low
Time Frame: Up to approximately 2.5 years
Secondary Outcomes
- Percentage of Participants with Adverse Events(Up to approximately 4 years)
- DoR in Participants with PIK3CA Amplification(Up to approximately 2.5 years)
- DoR in Participants with PTEN Loss/low(Up to approximately 2.5 years)
- Overall Survival (OS)(Up to approximately 2.5 years)
- OS in Participants with PIK3CA Amplification(Up to approximately 2.5 years)
- OS in Participants with PTEN Loss/low(Up to approximately 2.5 years)
- Objective Tumor Response(Up to approximately 2.5 years)
- Objective Tumor Response in Participants with PIK3CA Amplification(Up to approximately 2.5 years)
- Objective Tumor Response in Participants with PTEN Loss/low(Up to approximately 2.5 years)
- Duration of Objective Response (DoR)(Up to approximately 2.5 years)