Safety and Efficacy of Carboplatin/Paclitaxel and Carboplatin/Paclitaxel/Bevacizumab With and Without Pictilisib in Previously Untreated Advanced or Recurrent Non-small Cell Lung Cancer

Phase 2

Completed

• Conditions: Non-Small Cell Lung Cancer
• Interventions: Drug: pictilisib; Drug: Placebo; Drug: carboplatin; Drug: bevacizumab; Drug: paclitaxel

• Registration Number: NCT01493843
• Lead Sponsor: Genentech, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-12-14
• Study First Submitted QC: 2011-12-15
• Study First Posted: 2011-12-16
• Study Start: 2012-01-20
• Primary Completion: 2016-03-30
• Study Completion: 2016-03-30
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-21
• Last Update Posted: 2017-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 501

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: 340 mg pictilisib + CP	pictilisib	Participants with advanced (Stage IV) or recurrent squamous NSCLC will be administered 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P).
Arm A: 340 mg pictilisib + CP	carboplatin	Participants with advanced (Stage IV) or recurrent squamous NSCLC will be administered 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P).
Arm A: 340 mg pictilisib + CP	paclitaxel	Participants with advanced (Stage IV) or recurrent squamous NSCLC will be administered 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P).
Arm B: Placebo + CP	Placebo	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).
Arm D: Placebo + CPB	Placebo	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).
Arm F: Placebo + CPB	Placebo	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).
Arm C: 340 mg pictilisib + CPB	bevacizumab	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).
Arm B: Placebo + CP	paclitaxel	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).
Arm B: Placebo + CP	carboplatin	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).
Arm C: 340 mg pictilisib + CPB	carboplatin	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).
Arm C: 340 mg pictilisib + CPB	paclitaxel	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).
Arm D: Placebo + CPB	bevacizumab	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).
Arm D: Placebo + CPB	carboplatin	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).
Arm D: Placebo + CPB	paclitaxel	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).
Arm E: 260 mg pictilisib + CPB	carboplatin	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).
Arm E: 260 mg pictilisib + CPB	bevacizumab	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).
Arm E: 260 mg pictilisib + CPB	paclitaxel	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).
Arm F: Placebo + CPB	bevacizumab	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).
Arm F: Placebo + CPB	carboplatin	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).
Arm F: Placebo + CPB	paclitaxel	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).
Arm C: 340 mg pictilisib + CPB	pictilisib	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).
Arm E: 260 mg pictilisib + CPB	pictilisib	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).

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	Up to approximately 2.5 years
PFS in Participants with Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) Amplification	Up to approximately 2.5 years
PFS in Participants with Phosphatase and Tensin Homolog (PTEN) Loss/Low	Up to approximately 2.5 years

Secondary Outcome Measures

Name	Time	Method
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
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
Percentage of Participants with Adverse Events	Up to approximately 4 years

Trial Locations

Locations (120)

Alabama Oncology; 🇺🇸 Birmingham, Alabama, United States

Highlands Oncology Group; 🇺🇸 Rogers, Arkansas, United States

cCare; 🇺🇸 Encinitas, California, United States

Kaiser Permanente - Oakland; 🇺🇸 Oakland, California, United States

Desert Hematology Oncology Group; 🇺🇸 Rancho Mirage, California, United States

Kaiser Permanente - Roseville; 🇺🇸 Roseville, California, United States

Kaiser Permanente Sacramento Medical Center; 🇺🇸 Sacramento, California, United States

Southern CA Permanente Med Grp; 🇺🇸 San Diego, California, United States

Kaiser Permanente; 🇺🇸 San Francisco, California, United States

K. Permanente - Santa Clara; 🇺🇸 Santa Clara, California, United States

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