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

Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Phase II, Double-Blind, Placebo-Controlled, Randomized Study Evaluating the Safety and Efficacy of Carboplatin/Paclitaxel and Carboplatin/Paclitaxel/Bevacizumab With and Without GDC-0941 in Patients With Previously Untreated Advanced or Recurrent Non-small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01493843
• Other study ID #: GO27912
• Secondary ID: 2011-002893-21
• Status: Completed
• Phase: Phase 2
• First received: December 14, 2011
• Last updated: April 21, 2017
• Start date: January 20, 2012
• Est. completion date: March 30, 2016

Study information

• Verified date: April 2017
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 501
• Est. completion date: March 30, 2016
• Est. primary completion date: March 30, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• pictilisib
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.
• Placebo
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.
• bevacizumab
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.
• carboplatin
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.
• paclitaxel
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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Chile,  France,  Germany,  Hungary,  Israel,  Italy,  Netherlands,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)		Up to approximately 2.5 years
Primary	PFS in Participants with Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) Amplification		Up to approximately 2.5 years
Primary	PFS in Participants with Phosphatase and Tensin Homolog (PTEN) Loss/Low		Up to approximately 2.5 years
Secondary	Objective Tumor Response		Up to approximately 2.5 years
Secondary	Objective Tumor Response in Participants with PIK3CA Amplification		Up to approximately 2.5 years
Secondary	Objective Tumor Response in Participants with PTEN Loss/low		Up to approximately 2.5 years
Secondary	Duration of Objective Response (DoR)		Up to approximately 2.5 years
Secondary	DoR in Participants with PIK3CA Amplification		Up to approximately 2.5 years
Secondary	DoR in Participants with PTEN Loss/low		Up to approximately 2.5 years
Secondary	Overall Survival (OS)		Up to approximately 2.5 years
Secondary	OS in Participants with PIK3CA Amplification		Up to approximately 2.5 years
Secondary	OS in Participants with PTEN Loss/low		Up to approximately 2.5 years
Secondary	Percentage of Participants with Adverse Events		Up to approximately 4 years