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

Genentech

Status and phase: Completed; Phase 2

Conditions: Non-Small Cell Lung Cancer

Treatments: Drug: pictilisib; Drug: bevacizumab; Drug: paclitaxel; Drug: Placebo; Drug: carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01493843

2011-002893-21 (EudraCT Number)

GO27912

Details and patient eligibility

About

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.

Enrollment: 501 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

501 participants in 6 patient groups, including a placebo group

Arm A: 340 mg pictilisib + CP

Experimental group

Description:

Participants with advanced (Stage IV) or recurrent squamous NSCLC will be administered 340 mg pictilisib plus carboplatin (C) plus paclitaxel (P).

Treatment:

Drug: carboplatin

Drug: paclitaxel

Drug: pictilisib

Arm B: Placebo + CP

Placebo Comparator group

Description:

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).

Treatment:

Drug: carboplatin

Drug: paclitaxel

Drug: Placebo

Arm C: 340 mg pictilisib + CPB

Experimental group

Description:

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).

Treatment:

Drug: carboplatin

Drug: paclitaxel

Drug: bevacizumab

Drug: pictilisib

Arm D: Placebo + CPB

Placebo Comparator group

Description:

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).

Treatment:

Drug: carboplatin

Drug: paclitaxel

Drug: bevacizumab

Drug: Placebo

Arm E: 260 mg pictilisib + CPB

Experimental group

Description:

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).

Treatment:

Drug: carboplatin

Drug: paclitaxel

Drug: bevacizumab

Drug: pictilisib

Arm F: Placebo + CPB

Placebo Comparator group

Description:

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).

Treatment:

Drug: carboplatin

Drug: paclitaxel

Drug: bevacizumab

Drug: Placebo