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
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 501
- 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
- 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)
Franklin Square Hospital
🇺🇸Baltimore, Maryland, United States
Royal Melbourne Hospital; Hematology and Medical Oncology
🇦🇺Parkville, Victoria, Australia
Orszagos Koranyi TBC es Pulmonologiai Intezet
ðŸ‡ðŸ‡ºBudapest, Hungary
Veszprem Megyei Onkormanyzat Tudogyogyintezet
ðŸ‡ðŸ‡ºFarkasgyepu, Hungary
Zala Megyei Korhaz; Dept of Pulmonary Medicine
ðŸ‡ðŸ‡ºZalaegerszeg, Hungary
Kiev City Clinical Oncology Center
🇺🇦Kiev, Ukraine
State Oncology Regional Treatment-Diagnostic Center; Chemotherapy Department
🇺🇦Lviv, Ukraine
Zaporizhzhia Regional Clinical Oncology Dispensary; Zaporizhzhya State Medical University
🇺🇦Zaporizhzhya, Ukraine
Amphia Ziekenhuis
🇳🇱Breda, Netherlands
Regional Oncology Center
🇷🇺Chelyabinsk, Russian Federation
Rsrch Onc Inst of Rosmed Tech; n.a. prof. N.N. Petrov; Dept of Surgery
🇷🇺St. Petersburg, Russian Federation
Volyn Regional Oncology Dispensary
🇺🇦Lutsk, Ukraine
Hospital Univ Vall d'Hebron; Servicio de Oncologia
🇪🇸Barcelona, Spain
Universitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands
Royal Surrey County Hospital; St. Lukes Cancer Centre
🇬🇧Guildford, United Kingdom
Az. Osp. S. Luigi Gonzaga; Malattie Apparato Respiratorio 5 Ad Indirizzo Oncologico
🇮🇹Orbassano, Piemonte, Italy
Leicester Royal Infirmary; Dept. of Medical Oncology
🇬🇧Leicester, United Kingdom
Hospital Nuestra Señora de Sonsoles; servicio de Oncologia
🇪🇸Avila, Spain
Catharina-ziekenhuis; Longgeneeskunde en Tuberculose
🇳🇱Eindhoven, Netherlands
Hospital Universitario 12 de Octubre; Servicio de Oncologia
🇪🇸Madrid, Spain
Moscow city oncology hospital #62 of Moscow Healthcare Department
🇷🇺Moscow, Russian Federation
City Oncology Hospital; Chemotherapy Dept
🇷🇺Nizhny Novgorod, Russian Federation
Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
🇪🇸Barcelona, Spain
Ausl Di Bologna-Ospedale Bellaria;U.O. Oncologia Medica
🇮🇹Bologna, Emilia-Romagna, Italy
Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica
🇮🇹Aviano, Friuli-Venezia Giulia, Italy
ASST DI MONZA; Oncologia Medica
🇮🇹Monza, Lombardia, Italy
Centre Hospitalier de Villefranche sur Saone
🇫🇷Villefranche-sur-Saone, France
Instituto FIDES
🇦🇷La Plata, Argentina
Alabama Oncology
🇺🇸Birmingham, Alabama, United States
Highlands Oncology Group
🇺🇸Rogers, Arkansas, United States
cCare
🇺🇸Encinitas, California, United States
Kaiser Permanente Sacramento Medical Center
🇺🇸Sacramento, California, United States
Kaiser Permanente - Oakland
🇺🇸Oakland, California, United States
Kaiser Permanente - Roseville
🇺🇸Roseville, California, United States
Desert Hematology Oncology Group
🇺🇸Rancho Mirage, California, United States
K. Permanente - Santa Clara
🇺🇸Santa Clara, California, United States
Southern CA Permanente Med Grp
🇺🇸San Diego, California, United States
Kaiser Permanente
🇺🇸San Francisco, California, United States
Stockton Hema Onc Med Grp Inc
🇺🇸Stockton, California, United States
University Cancer & Blood Center, LLC
🇺🇸Athens, Georgia, United States
Florida Cancer Specialists (St. Petersburg - St. Anthony's Professional Building)
🇺🇸Saint Petersburg, Florida, United States
Kaiser Permanente - Vallejo
🇺🇸Vallejo, California, United States
Hematology Oncology PC; Bennett Cancer Center
🇺🇸Stamford, Connecticut, United States
K. Permanente - Walnut Creek
🇺🇸Walnut Creek, California, United States
Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)
🇺🇸Jacksonville, Florida, United States
Florida Cancer Specialists - Fort Myers (Colonial Center Dr)
🇺🇸Fort Myers, Florida, United States
Advanced Medical Specialties
🇺🇸Miami, Florida, United States
Peachtree Hematology & Oncology Consultants, Pc
🇺🇸Atlanta, Georgia, United States
Georgia Cancer Specialists
🇺🇸Atlanta, Georgia, United States
Hematology-Oncology of Indiana, Pc
🇺🇸Indianapolis, Indiana, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Massachusetts General Hospital.
🇺🇸Boston, Massachusetts, United States
Wayne State University; Hemat/Onc, 4HW CRC
🇺🇸Detroit, Michigan, United States
Dana Farber Cancer Inst.
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Va Sierra Nevada Health Care System
🇺🇸Reno, Nevada, United States
Roswell Park Cancer Inst.
🇺🇸Buffalo, New York, United States
San Juan Oncology Associates
🇺🇸Farmington, New Mexico, United States
Piedmont Hematology Oncology Associates
🇺🇸Winston-Salem, North Carolina, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
Univ Hosp Case Medical Center
🇺🇸Cleveland, Ohio, United States
Center for Biomedical Research LLC
🇺🇸Knoxville, Tennessee, United States
The Sarah Cannon Research Inst
🇺🇸Nashville, Tennessee, United States
Vanderbilt
🇺🇸Nashville, Tennessee, United States
Wellmonth Physician Services
🇺🇸Bristol, Virginia, United States
University of Texas M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Northwest Medical Specialties
🇺🇸Tacoma, Washington, United States
Blue Ridge Cancer Care - Roanoke
🇺🇸Roanoke, Virginia, United States
VA Puget Sound Health Care Sys
🇺🇸Seattle, Washington, United States
Clinica Universitaria Reina Fabiola
🇦🇷Cordoba, Argentina
Isis Centro Especializado de Luces; Oncology
🇦🇷Santa Fe, Argentina
Royal Prince Alfred Hospital; Sydney Cancer Centre
🇦🇺Camperdown, New South Wales, Australia
St Vincent'S Hospital
🇦🇺Darlinghurst, New South Wales, Australia
Calvary Mater Newcastle; Medical Oncology
🇦🇺Waratah, New South Wales, Australia
Footscray Hospital
🇦🇺Footscray, Victoria, Australia
Flinders Medical Centre; Medical Oncology
🇦🇺Bedford Park, South Australia, Australia
Royal Hobart Hospital; Medical Oncology
🇦🇺Hobart, Tasmania, Australia
Centro de Oncologia da Bahia - CENOB
🇧🇷Salvador, BA, Brazil
Clinica de Tratamento e Pesquisa Oncologica - Oncotek
🇧🇷Brasilia, DF, Brazil
Instituto Nacional de Cancer - INCa; Oncologia
🇧🇷Rio de Janeiro, RJ, Brazil
Liga Norte Riograndense Contra O Câncer
🇧🇷Natal, RN, Brazil
Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, RS, Brazil
Centro de Pesquisas Oncologicas - CEPON
🇧🇷Florianopolis, SC, Brazil
Hospital Mae de Deus
🇧🇷Porto Alegre, RS, Brazil
Hospital Amaral Carvalho
🇧🇷Jau, SP, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP
🇧🇷Sao Paulo, SP, Brazil
Instituto de Oncologia de Sorocaba - CEPOS
🇧🇷Sorocaba, SP, Brazil
Mcgill University - Royal Victoria Hospital; Oncology
🇨🇦Montreal, Quebec, Canada
Hopital du Sacre-Coeur
🇨🇦Montreal, Quebec, Canada
Fundacion Arturo Lopez Perez
🇨🇱Santiago, Chile
Clinica Santa Maria
🇨🇱Santiago, Chile
Instituto Oncologico del sur
🇨🇱Temuco, Chile
Hospital Clinico Vina del Mar
🇨🇱Viña del Mar, Chile
Hopital Morvan
🇫🇷Brest, France
Clinique Victor Hugo; Radiotherapie
🇫🇷Le Mans, France
Clinique Catherine de Sienne; Service de cancérologie
🇫🇷Nantes, France
Ico Rene Gauducheau; Oncologie
🇫🇷Saint Herblain, France
Institut Gustave Roussy; Departement Oncologie Medicale
🇫🇷Villejuif, France
Zentralklinik Bad Berka GmbH; Abteilung Onkologie und Hämatologie
🇩🇪Bad Berka, Germany
Asklepios-Fachkliniken Muenchen-Gauting; Onkologie
🇩🇪Gauting, Germany
Krankenhaus Grosshansdorf;Pneumologie & Thoraxchirurgie
🇩🇪Grosshansdorf, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Medizinische Klinik, Pneumologie
🇩🇪Mainz, Germany
Universitätsklinikum Regensburg; Klinik und Poliklinik für Innere Medizin II, Pneumologie
🇩🇪Regensburg, Germany
Schwarzwald-Baar Klinikum/VS GmbH; Onkologie/Hämatologie/Infektologie
🇩🇪Villingen-Schwenningen, Germany
St. Vincentius Kliniken Karlsruhe; Abteilung Hämatologie / Onkologie
🇩🇪Karlsruhe, Germany
Universitätsklinikum Ulm; Medizinische Uni-Klinik III Abt. Innere Medizin III Hämatologie u. Onkolo.
🇩🇪Ulm, Germany
Tudogyogyintezet Torokbalint
ðŸ‡ðŸ‡ºTorokbalint, Hungary
Shaare Zedek Medical Center; Oncology Dept
🇮🇱Jerusalem, Israel
Koch Robert Korhaz
ðŸ‡ðŸ‡ºEdeleny, Hungary
Vas Megyei Markusovszky Korhaz ; Pulmonology
ðŸ‡ðŸ‡ºSzombathely, Hungary
Meir Medical Center; Oncology
🇮🇱Kfar-Saba, Israel
A.O.U.I. VERONA-OSPEDALE POLICLINICO G.B. ROSSI BORGO ROMA;ONCOLOGIA MEDICA-d.U.
🇮🇹Verona, Veneto, Italy
Leningrad Regional Clinical Hospital
🇷🇺St Petersburg, Russian Federation
Hospital Universitario Puerta de Hierro; Servicio de Oncologia
🇪🇸Madrid, Spain
Sumy Reg. Clin. Oncological Dispensary; Thoracall Department
🇺🇦Sumy, Ukraine
Crimean Republican Institute; Oncology Clin Dispensary; Chemotherapy Dept
🇺🇦Simferopol, Ukraine
Christie Hospital Nhs Trust; Medical Oncology
🇬🇧Manchester, United Kingdom
The Christ Hospital
🇺🇸Cincinnati, Ohio, United States
Chaim Sheba Medical Center; Oncology Dept
🇮🇱Ramat Gan, Israel
Lynn Regional Cancer Center West
🇺🇸Boca Raton, Florida, United States