A Study of Bevacizumab in Combination With Standard of Care Treatment in Participants With Advanced Non-squamous Non-small Cell Lung Cancer (NSCLC)

Non-Squamous Non-Small Cell Lung Cancer Clinical Trial

Official title:

An Open-label, Randomized, Phase IIIb Trial Evaluating the Efficacy and Safety of Standard of Care +/- Continuous Bevacizumab Treatment Beyond Progression of Disease (PD) in Patients With Advanced Non-squamous Non-small Cell Lung Cancer (NSCLC) After First Line Treatment With Bevacizumab Plus a Platinum Doublet-containing Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01351415
• Other study ID #: MO22097
• Secondary ID: 2010-022645-14
• Status: Completed
• Phase: Phase 3
• First received: May 9, 2011
• Last updated: August 17, 2017
• Start date: June 25, 2011
• Est. completion date: June 25, 2016

Study information

• Verified date: August 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This open-label, randomized, multicenter study will evaluate the efficacy and safety of bevacizumab (Avastin) in combination with standard of care (SOC) treatment in participants with advanced non-squamous NSCLC. Participants will be enrolled at documentation of progression of disease (PD) after 4-6 cycles of first-line treatment with bevacizumab plus a platinum doublet-containing therapy and a minimum of two cycles of bevacizumab maintenance treatment prior to PD. Participants will be randomly assigned to one of two treatment arms to receive either bevacizumab plus SOC treatment or SOC treatment alone.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 485
• Est. completion date: June 25, 2016
• Est. primary completion date: June 25, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed non-squamous NSCLC

• Documented progression of disease (locally recurrent or metastatic) per investigator assessment following first-line treatment with 4-6 cycles of Bevacizumab plus a platinum doublet-containing chemotherapy regimen and a minimum of 2 cycles of Bevacizumab (monotherapy) maintenance treatment prior to first progression of disease

• No treatment interruption of Bevacizumab treatment greater than 2 consecutive cycles (42 days) between the start of first-line treatment to start of Cycle 1 of second line treatment

• Randomization within 4 weeks of progression of disease

• At least one unidimensionally measurable lesion meeting RECIST v1.1 criteria

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Participants with adequate hematological, liver, and renal function

• Female participants must not be pregnant or breast-feeding. Female participants of childbearing potential and fertile male participants must agree to use a highly effective contraceptive during the trial and for a period of at least 6 months following the last administration of trial drug(s)

Exclusion Criteria:

• Mixed, non-small cell and small cell tumors or mixed adenosquamous carcinomas with a predominant squamous component

• Epidermal growth factor receptor (EGFR)-mutation-positive disease according to local laboratory testing

• History of hemoptysis greater than or equal to (>/=) grade 2 within 3 months of randomization

• History or evidence of inherited bleeding diathesis or coagulopathy with a risk of bleeding and active gastrointestinal bleeding

• Major cardiac disease

• Treatment with any other investigational agent within 28 days prior to randomization

• Known hypersensitivity to bevacizumab or any of its excipients, or any SOC drugs foreseen

• Malignancy other than NSCLC within 5 years prior to randomization and evidence of any other disease that contraindicates the use of an investigational or SOC drug

Related Conditions & MeSH terms

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

Intervention

Drug:
• Bevacizumab
Participants will receive bevacizumab 7.5 or 15 milligrams per kilogram (mg/kg) intravenously.
• Docetaxel
Docetaxel 60 or 75 milligram per meter square (mg/m^2) on Day 1 every 21 days.
• Erlotinib
Erlotinib 150 mg daily taken on an empty stomach at least one hour before or two hours after the ingestion of food.
• Pemetrexed
Pemetrexed 500 mg/m^2 IV over 10 minutes on Day 1 every 21 days.

Locations

Country	Name	City	State
Argentina	Inst. Alexander Fleming; Oncology Dept	Buenos Aires
Argentina	Centro Oncologico Infinito; Oncologia	La Pampa
Argentina	Hospital Privado de Comunidad; Oncology	Mar Del Plata
Argentina	Sanatorio Parque de Rosario	Rosario
Argentina	ISIS Clinica Especializada	Santa Fe
Argentina	Clínica Viedma	Viedma, Rio Negro
Austria	LKH Hohenems; Abteilung für Pulmologie	Hohenems
Austria	Tiroler Landeskrankenanstalten Ges.M.B.H.; Innere Medizin Abt. Für Hämatologie & Onkologie	Innsbruck
Austria	Lkh Natters; Abt. Für Atemwegs- & Lungenkrankheiten	Natters
Austria	A.Ö. LKH; Abt. für Lungenkrankheiten	Steyr
Austria	Klinikum Wels-Grieskirchen; Lungenabt.	Wels
Austria	Krankenhaus Der Stadt Wien Lainz; V. Medizinische Abt.	Wien
Austria	Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Abt. für Onkologie	Wien
Austria	SMZ - Baumgartner Hohe, Pavilion Leopold; 1.Interne Lungenabteilung, Onkologische Tagesklinik	Wien
Belgium	Clin. Europe (Ste Elisabeth)	Bruxelles
Brazil	Centro de Estudos e Pesquisas Oncologicas - CESPO	Brasilia	DF
Brazil	Sociedade beneficente de senhoras Hospital Sirio Libanes	Brasilia	DF
Brazil	Centro de Pesquisa Clínica- Instituto do Câncer do Ceará- ICC	Fortaleza	CE
Brazil	Hospital de Caridade de Ijui; Oncologia	Ijui	RS
Brazil	Clinica de Neoplasias Litoral	Itajai	SC
Brazil	Clinicas Oncologicas Integradas - COI	Rio de Janeiro	RJ
Brazil	Nucleo de Oncologia da Bahia - NOB	Salvador, Bahia	BA
Brazil	Hospital A. C. Camargo; Oncologia	Sao Paulo	SP
Brazil	Hospital Sao Jose	São Paulo	SP
Brazil	Instituto de Câncer de Brasília	Taguatinga	DF
Denmark	Nordsjællands Hospital, Hillerød, Onkologisk Afdeling	Hillerod
France	Poly Parc Rambot La Provencale; Chimiotherapie Ambulatoire	Aix En Provence
France	Centre Francois Baclesse; Oncologie	Caen
France	Centre Hospitalier Intercommunal; Service de Pneumologie	Creteil
France	Hopital Nord Ouest;Unite 2c	Gleize
France	Centre Oscar Lambret	Lille
France	Hopital Calmette; Pneumologie	Lille
France	Hopital Louis Pradel; Cardiologie B	Lyon
France	Hopital Nord; Service d'Oncologie Multidisciplinaire et Innovation Thérapeutique	Marseille
France	Hôpital Saint Joseph; Oncologie Medicale	Marseille
France	Centre Antoine Lacassagne	Nice
France	Ch Lyon Sud; Chir Onc Gyne Sct Jules Courmont	Pierre Benite
France	CH Rene Dubos; Oncologie	Pontoise
France	Ico Rene Gauducheau; Oncologie	Saint Herblain
France	Institut de Cancérologie de Loire	St-Priest-En-Jarez
France	Centre Paul Strauss; Oncologie Medicale	Strasbourg
France	Hia Sainte Anne; Pneumologie	Toulon
France	Hopital Sainte Musse; Pneumologie	Toulon
France	Clinique Pasteur; Pneumologie	Toulouse
France	Chi De La Haute Saone De Vesoul; Pneumologie	Vesoul
Germany	Zentralklinik Bad Berka GmbH; Pneumologie	Bad Berka
Germany	Praxis Dr. med. David Borquez	Bergisch Gladbach
Germany	Klinikum Esslingen; Klinik für Kardiologie, Angiologie und Pneumologie	Esslingen
Germany	Krankenhaus Nordwest; Klinik f. Onkologie und Hämatologie	Frankfurt
Germany	SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie	Gera
Germany	LungenClinic Großhansdorf	Großhansdorf
Germany	Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin I	Halle (Saale)
Germany	Universitaetsklinikum des Saarlandes; Innere Medizin V	Homburg/Saar
Germany	Fachklinik für Lungenerkrankungen	Immenhausen
Germany	St. Vincentius Kliniken Karlsruhe; Abteilung Hämatologie / Onkologie	Karlsruhe
Germany	Praxis Christian Geßner	Leipzig
Germany	Robert-Koch-Klinik; Pneumologie	Leipzig
Germany	Johannes-Wesling-Klinikum Minden; Onkologische Ambulanz / Tagesklinik	Minden
Germany	Ludwig-Maximilians Uni Klinik Innenstadt; Medizinische Klinik	Muenchen
Germany	Pius-Hospital; Klinik fuer Haematologie und Onkologie	Oldenburg
Greece	Sotiria Hospital	Athens
Greece	Metropolitan Hospital; 2Nd Oncology Clinic	Piraeus
Greece	Diavalkaniko Hospital	Thessaloniki
Greece	General Hospital of Thessaloniki Papanikolaou; Uni Pneumonology Dept.	Thessaloniki
Italy	Citta Ospedaliera; Divisione Oncologia Medica	Avellino	Campania
Italy	IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A	Genova	Liguria
Italy	IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A	Napoli	Campania
Italy	A.O. Universitaria Pisana-Ospedale Cisanello; Dipartimento Cardio Toracico-Pneumologia Ii	Pisa	Toscana
Italy	Azienda Ospedaliera San Camillo Forlanini; U.O.C. Pneumologia Ad Indirizzo Oncologico 1	Roma	Lazio
Italy	Policlinico Universitario Campus Biomedico; Uoc Oncologia Medica	Roma	Lazio
Italy	Az. Osp. Di Busto P.O. Di Saronno; U.O. Di Oncologia Medica	Saronno	Lombardia
Japan	Aichi Cancer Center Hospital; Respiratory Medicine	Aichi
Japan	National Cancer Center Hospital East; Thoracic Oncology	Chiba
Japan	National Hospital Organization Shikoku Cancer Center; Thoracic Oncology	Ehime
Japan	National Hospital Organization Kyushu Cancer Center, Thoracic Oncology	Fukuoka
Japan	Hyogo Cancer Center; Thoracic Oncology	Hyogo
Japan	Kanagawa Cardiovascular and Respiratory Center; Respiratory Medicine	Kanagawa
Japan	Yokohama Municipal Citizen'S Hospital; Respiratory	Kanagawa
Japan	Miyagi Cancer Center; Respiratory Medicine	Miyagi
Japan	Okayama University Hospital; Respiratory and Allergy Medicine	Okayama
Japan	OSAKA CITY GENERAL HOSPITAL;Medical Oncology	Osaka
Japan	Osaka International Cancer Institute; Thoracic Oncology	Osaka
Japan	Shizuoka Cancer Center; Thoracic Oncology	Shizuoka
Japan	National Cancer Center Hospital; Thoracic Medical Oncology	Tokyo
Japan	The Cancer Institute Hospital of JFCR, Respiratory Medicine	Tokyo
Lebanon	American University of Beirut - Medical Center	Beirut
Lebanon	Hotel Dieu de France; Oncology	Beirut
Lebanon	Middle East Inst. of Health; Oncology	Beirut
Mexico	Centenario Hospital Miguel Hidalgo	Aguascalientes
Mexico	Centro Médico Abc the American British Cowdray Medical Center, I.A.P. - Centro de Cáncer	Mexico City
Mexico	Hospital Central Sur de Alta Especialidad Petróleos Mexicanos	Mexico City
Netherlands	Amphia Ziekenhuis; Afdeling Longziekten	Breda
Netherlands	Leyenburg Hospital; Pulmonology	Den Haag
Netherlands	Catharina Ziekenhuis; Dept of Lung Diseases	Eindhoven
Netherlands	Ziekenhuis St Jansdal; Dept of Lung Diseases	Harderwijk
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Netherlands	Antonius Ziekenhuis; Dept of Lung Diseases	Nieuwegein
Oman	College of Medicine & Sciences, Sultan Qaboos University Hospital	Muscat
Slovakia	Fnsp Fdr Banska Bystrica; Dep of Pneumology&Ftizeology	Banska Bystrica
Slovakia	FNsP Bratislava, Nemocnica Ruzinov	Bratislava
Slovakia	Vychodoslovensky onkologicky ustav	Kosice
Slovakia	Inst. of Tb & Respiratory Diseases; Dep. of Oncology	Nitra
Spain	Hospital General Univ. de Alicante; Servicio de Oncologia	Alicante
Spain	Hospital de Cruces; Servicio de Oncologia	Barakaldo	Vizcaya
Spain	Centro Oncologico MD Anderson International Espana	Madrid
Spain	Hospital Universitario Clínico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia
Spain	Hospital Universitario Dr. Peset; Servicio de Oncologia	Valencia
Spain	Hospital Universitario Miguel Servet; Servicio Oncologia	Zaragoza
United Arab Emirates	Tawam Hospital; Medical Oncology Department	Al Ain
United States	McFarland Clinic	Ames	Iowa
United States	Ann Arbor Hematology Oncology	Ann Arbor	Michigan
United States	Anne Arundel Health System Research Instit-Annapolis Oncology Ctr	Annapolis	Maryland
United States	Fox Valley Hema and Onc SC	Appleton	Wisconsin
United States	Emory Univ Winship Cancer Inst	Atlanta	Georgia
United States	Hematology/Oncology Clinic, LLP	Baton Rouge	Louisiana
United States	St. Lukes Hospital and Health Network	Bethlehem	Pennsylvania
United States	Lynn Cancer Institute - West	Boca Raton	Florida
United States	Tufts Medical Center; Neely Cancer Center	Boston	Massachusetts
United States	East Valley Hematology ; Oncology Medical Group	Burbank	California
United States	Aultman Hospital	Canton	Ohio
United States	Mid Ohio Onc Hematology Inc	Columbus	Ohio
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Unv of TX SW Med Cntr; Hematology/Onc	Dallas	Texas
United States	Dayton Clinical Oncology Prog	Dayton	Ohio
United States	Henry Ford Hospital; Hematology Oncology	Detroit	Michigan
United States	Hematology & Oncology Assoc; North Eastern Pennsylvania	Dunmore	Pennsylvania
United States	Alexian Brothers Neurosci Inst	Elk Grove Village	Illinois
United States	California Cancer Associates for Research & Excellence, Inc.	Encinitas	California
United States	Oncology-Evanston Nthwest Healthcare Kellogg Cancer Care Ctr	Evanston	Illinois
United States	West Clinic	Germantown	Tennessee
United States	Arizona Center for Cancer Care	Glendale	Arizona
United States	Palo Verde Hema/Onc	Glendale	Arizona
United States	Cancer & Hematology Center of West Michigan	Grand Rapids	Michigan
United States	Carolina Oncology Specialists, PA - Hickory	Hickory	North Carolina
United States	St. Francis Medical Group	Indianapolis	Indiana
United States	Baptist - MD Anderson Cancer Center	Jacksonville	Florida
United States	Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)	Jacksonville	Florida
United States	Joliet Oncology Hematology Associates, Ltd.	Joliet	Illinois
United States	Clopton Clinic	Jonesboro	Arkansas
United States	University of Tennessee Medical Center Cancer Institute	Knoxville	Tennessee
United States	Gundersen Lutheran	La Crosse	Wisconsin
United States	Scripps Clinic; Hematology & Oncology	La Jolla	California
United States	Louisiana Oncology Associates	Lafayette	Louisiana
United States	St. Mary Medical Center	Langhorne	Pennsylvania
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	Jewish Cancer Care	Louisville	Kentucky
United States	UNI OF WISCONSIN SCHOOL OF MEDICINE; GI Oncology Research Group, Paul P Carbone Cancer Center	Madison	Wisconsin
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Signal Point Clinical; Research Center, LLC	Middletown	Ohio
United States	USA Mitchell Cancer Institute	Mobile	Alabama
United States	The Hospital of Central CT	New Britain	Connecticut
United States	Oncology Hematology Associates of Southwest Indiana	Newburgh	Indiana
United States	Cancer Care & Hematology; Specialists of Chicagoland	Niles	Illinois
United States	Eastern Ct Hema/Onco Assoc; Dept of Oncology	Norwich	Connecticut
United States	Memorial Hospital of Rhode Island	Pawtucket	Rhode Island
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pennsylvania; Radiation Oncology	Philadelphia	Pennsylvania
United States	Delta Hematology/ Oncology Associates	Portsmouth	Virginia
United States	Kootenai Cancer Center	Post Falls	Idaho
United States	W. Suburban Ctr for Cncer Care	River Forest	Illinois
United States	Blue Ridge Cancer Care - Roanoke	Roanoke	Virginia
United States	Cancer Care Centers of Brevard	Rockledge	Florida
United States	Sutter Cancer Center	Sacramento	California
United States	St Joseph Oncology	Saint Joseph	Missouri
United States	Heartland CCOP/Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Metro-Minnesota CCOP	Saint Louis Park	Minnesota
United States	Coastal Integrative Cancer Care	San Luis Obispo	California
United States	Summit Cancer Care PC	Savannah	Georgia
United States	New England Cancer Specialists	Scarborough	Maine
United States	Medical Oncology Associates	Spokane	Washington
United States	Stony Brook Univ Cancer Ctr; Medical Oncology Clinic	Stony Brook	New York
United States	Toledo Hospital; CCOP Toledo	Toledo	Ohio
United States	Innovative Clinical Research Institute	Whittier	California
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Lankenau Hospital	Wynnewood	Pennsylvania
United States	York Hospital	York	Maine

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Brazil,  Denmark,  France,  Germany,  Greece,  Italy,  Japan,  Lebanon,  Mexico,  Netherlands,  Oman,  Slovakia,  Spain,  United Arab Emirates, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Overall survival (OS) was defined as the time from the date of randomization at first progression of disease to the date of death, regardless of the cause of death.	Up to data cut-off date 24 June 2016 (approximately 5 years)
Secondary	Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	PFS was defined as the time from start of treatment to the first event of death or PD. Tumor response was assessed by the IRF according to RECIST v1.1. Disease progression or PD was defined as =20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PFS2 is defined as the time between randomization at PD1 and the date of PD2 or death, whichever occurs first. PFS3 is defined as the time between PD2 and the date of PD3 or death, whichever occurs first.	Up to data cut-off date 24 June 2016 (approximately 5 years)
Secondary	Percentage of Participants With Objective Response According to RECIST v1.1	The objective response is defined as complete response (CR) or partial response (PR) assessed according to the RECIST v.1.1 criteria with baseline tumour assessment as the reference. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as greater than or equal to (=) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. Response was to be confirmed =4 weeks after the initial assessment of CR or PR.	Up to data cut-off date 24 June 2016 (approximately 5 years)
Secondary	Percentage of Participants With Disease Control According to RECIST v1.1	The disease control rate is defined as CR or PR or stable disease (SD) assessed according to the RECIST v.1.1 criteria with baseline tumour assessment as the reference. SD was defined as neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since treatment started for target lesions and the persistence of 1 or more non-target lesions.	Up to data cut-off date 24 June 2016 (approximately 5 years)
Secondary	Duration of Response (DoR) According to RECIST v1.1	Duration of response is defined as the time that measurement criteria are met for objective response (CR/PR) (whichever status is recorded first) until the first date of progression or death is documented. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than < 10 mm. PR was defined as greater than or equal to =30 % decrease in sum of longest diameter of target lesions in reference to baseline sum longest diameter.	Up to data cut-off date 24 June 2016 (approximately 5 years)
Secondary	Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant.	Up to data cut-off date 24 June 2016 (approximately 5 years)
Secondary	Time to Progression (TTP) According to RECIST v1.1	The time to progression was defined as the time from baseline until disease progression as determined by the RECIST v1.1. TTP2 is defined as the interval between the day of randomization at PD1 and PD2. TTP3 is defined as the interval between the day of PD2 and PD3. PD was defined as =20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	Up to data cut-off date 24 June 2016 (approximately 5 years)
Secondary	Percentage of Participants Who Are Alive at Month 6, 12, and 18	Percentage of participants who were alive at Month 6, 12 and 18 were reported.	Month 6, 12, 18