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

NCT01493843 | Completed Phase 2 FDA Drug

• 2 other identifiers: GO279122011-002893-21
• Study Type: interventional
• Target: 501
• Locations: 16 countries
• Sites: 120

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.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (10)

• 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

Study Arms (6)

Arm A: 340 mg pictilisib + CP

EXPERIMENTAL

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

Drug: pictilisib; Drug: carboplatin; Drug: paclitaxel

Arm B: Placebo + CP

PLACEBO COMPARATOR

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).

Drug: Placebo; Drug: carboplatin; Drug: paclitaxel

Arm C: 340 mg pictilisib + CPB

EXPERIMENTAL

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).

Drug: pictilisib; Drug: bevacizumab; Drug: carboplatin; Drug: paclitaxel

Arm D: Placebo + CPB

PLACEBO COMPARATOR

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).

Drug: Placebo; Drug: bevacizumab; Drug: carboplatin; Drug: paclitaxel

Arm E: 260 mg pictilisib + CPB

EXPERIMENTAL

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).

Drug: pictilisib; Drug: bevacizumab; Drug: carboplatin; Drug: paclitaxel

Arm F: Placebo + CPB

PLACEBO COMPARATOR

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).

Drug: Placebo; Drug: bevacizumab; Drug: carboplatin; Drug: paclitaxel

Interventions

pictilisib DRUG

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.

Also known as: GDC-0941

Arm A: 340 mg pictilisib + CP; Arm C: 340 mg pictilisib + CPB; Arm E: 260 mg pictilisib + CPB

Placebo DRUG

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.

Arm B: Placebo + CP; Arm D: Placebo + CPB; Arm F: Placebo + CPB

bevacizumab DRUG

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.

Also known as: Avastin

Arm C: 340 mg pictilisib + CPB; Arm D: Placebo + CPB; Arm E: 260 mg pictilisib + CPB; Arm F: Placebo + CPB

carboplatin DRUG

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.

Arm A: 340 mg pictilisib + CP; Arm B: Placebo + CP; Arm C: 340 mg pictilisib + CPB; Arm D: Placebo + CPB; Arm E: 260 mg pictilisib + CPB; Arm F: Placebo + CPB

paclitaxel DRUG

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.

Arm A: 340 mg pictilisib + CP; Arm B: Placebo + CP; Arm C: 340 mg pictilisib + CPB; Arm D: Placebo + CPB; Arm E: 260 mg pictilisib + CPB; Arm F: Placebo + CPB

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (120)

Alabama Oncology

Birmingham, Alabama, 35211, United States

Location

Highlands Oncology Group

Rogers, Arkansas, 72758, United States

Location

cCare

Encinitas, California, 92024, United States

Location

Kaiser Permanente - Oakland

Oakland, California, 94611, United States

Location

Desert Hematology Oncology Group

Rancho Mirage, California, 92270, United States

Location

Kaiser Permanente - Roseville

Roseville, California, 95661, United States

Location

Kaiser Permanente Sacramento Medical Center

Sacramento, California, 95825, United States

Location

Southern CA Permanente Med Grp

San Diego, California, 92120, United States

Location

Kaiser Permanente

San Francisco, California, 94115, United States

Location

K. Permanente - Santa Clara

Santa Clara, California, 95051, United States

Location

Stockton Hema Onc Med Grp Inc

Stockton, California, 95204, United States

Location

Kaiser Permanente - Vallejo

Vallejo, California, 94589, United States

Location

K. Permanente - Walnut Creek

Walnut Creek, California, 94596, United States

Location

Hematology Oncology PC; Bennett Cancer Center

Stamford, Connecticut, 06902, United States

Location

Lynn Regional Cancer Center West

Boca Raton, Florida, 33486, United States

Location

Florida Cancer Specialists - Fort Myers (Colonial Center Dr)

Fort Myers, Florida, 33905, United States

Location

Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)

Jacksonville, Florida, 32256, United States

Location

Advanced Medical Specialties

Miami, Florida, 33176, United States

Location

Florida Cancer Specialists (St. Petersburg - St. Anthony's Professional Building)

St. Petersburg, Florida, 33705, United States

Location

University Cancer & Blood Center, LLC

Athens, Georgia, 30607, United States

Location

Peachtree Hematology & Oncology Consultants, Pc

Atlanta, Georgia, 30318, United States

Location

Georgia Cancer Specialists

Atlanta, Georgia, 30341, United States

Location

Hematology-Oncology of Indiana, Pc

Indianapolis, Indiana, 46260, United States

Location

Franklin Square Hospital

Baltimore, Maryland, 21237, United States

Location

Massachusetts General Hospital.

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Inst.

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Wayne State University; Hemat/Onc, 4HW CRC

Detroit, Michigan, 48201, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Va Sierra Nevada Health Care System

Reno, Nevada, 89502, United States

Location

San Juan Oncology Associates

Farmington, New Mexico, 87401, United States

Location

Roswell Park Cancer Inst.

Buffalo, New York, 14263, United States

Location

Piedmont Hematology Oncology Associates

Winston-Salem, North Carolina, 27103, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

Univ Hosp Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Center for Biomedical Research LLC

Knoxville, Tennessee, 37909, United States

Location

The Sarah Cannon Research Inst

Nashville, Tennessee, 37203, United States

Location

Vanderbilt

Nashville, Tennessee, 37232, United States

Location

University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Wellmonth Physician Services

Bristol, Virginia, 24201, United States

Location

Blue Ridge Cancer Care - Roanoke

Roanoke, Virginia, 24014, United States

Location

VA Puget Sound Health Care Sys

Seattle, Washington, 98108, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

Clinica Universitaria Reina Fabiola

Córdoba, X5004FHP, Argentina

Location

Instituto FIDES

La Plata, B1900BAJ, Argentina

Location

Isis Centro Especializado de Luces; Oncology

Santa Fe, 03000, Argentina

Location

Royal Prince Alfred Hospital; Sydney Cancer Centre

Camperdown, New South Wales, 2050, Australia

Location

St Vincent'S Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

Calvary Mater Newcastle; Medical Oncology

Waratah, New South Wales, 2298, Australia

Location

Flinders Medical Centre; Medical Oncology

Bedford Park, South Australia, 5042, Australia

Location

Royal Hobart Hospital; Medical Oncology

Hobart, Tasmania, 7000, Australia

Location

Footscray Hospital

Footscray, Victoria, 3011, Australia

Location

Royal Melbourne Hospital; Hematology and Medical Oncology

Parkville, Victoria, 3052, Australia

Location

Centro de Oncologia da Bahia - CENOB

Salvador, Estado de Bahia, 41820-021, Brazil

Location

Clinica de Tratamento e Pesquisa Oncologica - Oncotek

Brasília, Federal District, 70390-055, Brazil

Location

Instituto Nacional de Cancer - INCa; Oncologia

Rio de Janeiro, Rio de Janeiro, 20560-120, Brazil

Location

Liga Norte Riograndense Contra O Câncer

Natal, Rio Grande do Norte, 59040150, Brazil

Location

Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

Location

Hospital Mae de Deus

Porto Alegre, Rio Grande do Sul, 90110-270, Brazil

Location

Centro de Pesquisas Oncologicas - CEPON

Florianópolis, Santa Catarina, 88034-000, Brazil

Location

Hospital Amaral Carvalho

Jaú, São Paulo, 17210-080, Brazil

Location

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, 01246-000, Brazil

Location

Instituto de Oncologia de Sorocaba - CEPOS

Sorocaba, São Paulo, 18030-245, Brazil

Location

Mcgill University - Royal Victoria Hospital; Oncology

Montreal, Quebec, H3A 1A1, Canada

Location

Hopital du Sacre-Coeur

Montreal, Quebec, J4B 5Z7, Canada

Location

Clinica Santa Maria

Santiago, 0, Chile

Location

Fundacion Arturo Lopez Perez

Santiago, 7500921, Chile

Location

Instituto Oncologico del sur

Temuco, 4810469, Chile

Location

Hospital Clinico Vina del Mar

Viña del Mar, 2520612, Chile

Location

Hopital Morvan

Brest, 29200, France

Location

Clinique Victor Hugo; Radiotherapie

Le Mans, 72015, France

Location

Clinique Catherine de Sienne; Service de cancérologie

Nantes, 44202, France

Location

Ico Rene Gauducheau; Oncologie

Saint-Herblain, 44805, France

Location

Centre Hospitalier de Villefranche sur Saone

Villefranche-sur-Saône, 69655, France

Location

Institut Gustave Roussy; Departement Oncologie Medicale

Villejuif, 94805, France

Location

Zentralklinik Bad Berka GmbH; Abteilung Onkologie und Hämatologie

Bad Berka, 99437, Germany

Location

Asklepios-Fachkliniken Muenchen-Gauting; Onkologie

Gauting, 82131, Germany

Location

Krankenhaus Grosshansdorf;Pneumologie & Thoraxchirurgie

Großhansdorf, 22927, Germany

Location

St. Vincentius Kliniken Karlsruhe; Abteilung Hämatologie / Onkologie

Karlsruhe, 76137, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Medizinische Klinik, Pneumologie

Mainz, 55131, Germany

Location

Universitätsklinikum Regensburg; Klinik und Poliklinik für Innere Medizin II, Pneumologie

Regensburg, 93053, Germany

Location

Universitätsklinikum Ulm; Medizinische Uni-Klinik III Abt. Innere Medizin III Hämatologie u. Onkolo.

Ulm, 89081, Germany

Location

Schwarzwald-Baar Klinikum/VS GmbH; Onkologie/Hämatologie/Infektologie

Villingen-Schwenningen, 78052, Germany

Location

Orszagos Koranyi TBC es Pulmonologiai Intezet

Budapest, 1121, Hungary

Location

Koch Robert Korhaz

Edelény, 3780, Hungary

Location

Veszprem Megyei Onkormanyzat Tudogyogyintezet

Farkasgyepű, 8582, Hungary

Location

Vas Megyei Markusovszky Korhaz ; Pulmonology

Szombathely, 9700, Hungary

Location

Tudogyogyintezet Torokbalint

Törökbálint, 2045, Hungary

Location

Zala Megyei Korhaz; Dept of Pulmonary Medicine

Zalaegerszeg, 8900, Hungary

Location

Shaare Zedek Medical Center; Oncology Dept

Jerusalem, 91031, Israel

Location

Meir Medical Center; Oncology

Kfar Saba, 4428164, Israel

Location

Chaim Sheba Medical Center; Oncology Dept

Ramat Gan, 5262100, Israel

Location

Ausl Di Bologna-Ospedale Bellaria;U.O. Oncologia Medica

Bologna, Emilia-Romagna, 40139, Italy

Location

Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica

Aviano, Friuli Venezia Giulia, 33081, Italy

Location

ASST DI MONZA; Oncologia Medica

Monza, Lombardy, 20900, Italy

Location

Az. Osp. S. Luigi Gonzaga; Malattie Apparato Respiratorio 5 Ad Indirizzo Oncologico

Orbassano, Piedmont, 10043, Italy

Location

A.O.U.I. VERONA-OSPEDALE POLICLINICO G.B. ROSSI BORGO ROMA;ONCOLOGIA MEDICA-d.U.

Verona, Veneto, 37134, Italy

Location

Amphia Ziekenhuis

Breda, 4818 CK, Netherlands

Location

Catharina-ziekenhuis; Longgeneeskunde en Tuberculose

Eindhoven, 5623 EJ, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, 9700 RB, Netherlands

Location

Regional Oncology Center

Chelyabinsk, 454087, Russia

Location

Moscow city oncology hospital #62 of Moscow Healthcare Department

Moscow, 143423, Russia

Location

City Oncology Hospital; Chemotherapy Dept

Nizhny Novgorod, 603000, Russia

Location

Rsrch Onc Inst of Rosmed Tech; n.a. prof. N.N. Petrov; Dept of Surgery

Saint Petersburg, 189646, Russia

Location

Leningrad Regional Clinical Hospital

Saint Petersburg, 194291, Russia

Location

Hospital Nuestra Señora de Sonsoles; servicio de Oncologia

Ávila, 05071, Spain

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, 08035, Spain

Location

Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia

Barcelona, 08916, Spain

Location

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, 28041, Spain

Location

Hospital Universitario Puerta de Hierro; Servicio de Oncologia

Madrid, 28222, Spain

Location

Kiev City Clinical Oncology Center

Kiev, 03115, Ukraine

Location

Volyn Regional Oncology Dispensary

Lutsk, 43018, Ukraine

Location

State Oncology Regional Treatment-Diagnostic Center; Chemotherapy Department

Lviv, 79031, Ukraine

Location

Crimean Republican Institute; Oncology Clin Dispensary; Chemotherapy Dept

Simferopol, 95023, Ukraine

Location

Sumy Reg. Clin. Oncological Dispensary; Thoracall Department

Sumy, 40005, Ukraine

Location

Zaporizhzhia Regional Clinical Oncology Dispensary; Zaporizhzhya State Medical University

Zaporizhzhya, 69040, Ukraine

Location

Royal Surrey County Hospital; St. Lukes Cancer Centre

Guildford, GU2 7XX, United Kingdom

Location

Leicester Royal Infirmary; Dept. of Medical Oncology

Leicester, LE1 5WW, United Kingdom

Location

Christie Hospital Nhs Trust; Medical Oncology

Manchester, M2O 4BX, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine; Bevacizumab; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2011
• First Posted: December 16, 2011
• Study Start: January 20, 2012
• Primary Completion: March 30, 2016
• Study Completion: March 30, 2016
• Last Updated: April 25, 2017

Record last verified: 2017-04

Locations

RU (5); AR (3); BR (10); IL (3); CA (2); HU (6); US (44); UA (6); GB (3); ES (5); AU (7); NL (3); FR (6); CL (4); IT (5); DE (8)