Non-Small Cell Lung Cancer
Conditions
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.
Interventions
DRUGpictilisib
Pictilisib, 260 milligrams (mg) or 340 mg, will be taken orally once daily on Days 1-14 of a 21-day cycle for four cycles. Starting with Cycle 5, pictilisib will be taken once daily continuously.
DRUGPlacebo
Placebo corresponding to 260 mg or 340 mg pictilisib will be taken orally once daily on Days 1-14 of a 21-day cycle for four cycles. Starting with Cycle 5, placebo will be taken once daily continuously.
DRUGbevacizumab
Bevacizumab, 15 milligrams per kilogram (mg/kg) will be administered intravenously (IV) at Day 1 of each 21-day cycle for a maximum of 34 cycles.
DRUGcarboplatin
Carboplatin will be administered IV to achieve an initial target area under the concentration curve (AUC) of 6 milligrams per milliliter per minute (mg/mL per min) on Day 1 of each 21-day cycle for a maximum of four cycles.
DRUGpaclitaxel
Paclitaxel will be administered at 200 milligrams per square meter (mg/m\^2) IV on Day 1 of each 21-day cycle for a maximum of four cycles.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| Objective Tumor Response | 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 |
| Overall Survival (OS) | 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 |
Countries
Argentina, Australia, Brazil, Canada, Chile, France, Germany, Hungary, Israel, Italy, Netherlands, Russia, Spain, Ukraine, United Kingdom, United States
Outcome results
None listed