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

Primary Purpose

Non-Squamous Non-Small Cell Lung Cancer

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Bevacizumab

Docetaxel

Erlotinib

Pemetrexed

About this trial

This is an interventional treatment trial for Non-Squamous Non-Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

USA Mitchell Cancer Institute
Palo Verde Hema/Onc
Arizona Center for Cancer Care
Clopton Clinic
East Valley Hematology ; Oncology Medical Group
California Cancer Associates for Research & Excellence, Inc.
Scripps Clinic; Hematology & Oncology
Sutter Cancer Center
Coastal Integrative Cancer Care
Innovative Clinical Research Institute
The Hospital of Central CT
Eastern Ct Hema/Onco Assoc; Dept of Oncology
Lynn Cancer Institute - West
Baptist - MD Anderson Cancer Center
Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)
Mount Sinai Medical Center
Cancer Care Centers of Brevard
Emory Univ Winship Cancer Inst
Summit Cancer Care PC
Kootenai Cancer Center
Alexian Brothers Neurosci Inst
Oncology-Evanston Nthwest Healthcare Kellogg Cancer Care Ctr
Joliet Oncology Hematology Associates, Ltd.
Cancer Care & Hematology; Specialists of Chicagoland
W. Suburban Ctr for Cncer Care
St. Francis Medical Group
Oncology Hematology Associates of Southwest Indiana
McFarland Clinic
Cancer Center of Kansas
University of Kentucky Medical Center
Jewish Cancer Care
Hematology/Oncology Clinic, LLP
Louisiana Oncology Associates
New England Cancer Specialists
York Hospital
Anne Arundel Health System Research Instit-Annapolis Oncology Ctr
Tufts Medical Center; Neely Cancer Center
Ann Arbor Hematology Oncology
Henry Ford Hospital; Hematology Oncology
Cancer & Hematology Center of West Michigan
Metro-Minnesota CCOP
St Joseph Oncology
Heartland CCOP/Missouri Baptist Medical Center
Stony Brook Univ Cancer Ctr; Medical Oncology Clinic
Carolina Oncology Specialists, PA - Hickory
Aultman Hospital
Mid Ohio Onc Hematology Inc
Dayton Clinical Oncology Prog
Signal Point Clinical; Research Center, LLC
Toledo Hospital; CCOP Toledo
Bay Area Hospital
St. Lukes Hospital and Health Network
Hematology & Oncology Assoc; North Eastern Pennsylvania
St. Mary Medical Center
University of Pennsylvania; Radiation Oncology
University of Pennsylvania
Temple University Hospital
Lankenau Hospital
Memorial Hospital of Rhode Island
West Clinic
University of Tennessee Medical Center Cancer Institute
Unv of TX SW Med Cntr; Hematology/Onc
Delta Hematology/ Oncology Associates
Blue Ridge Cancer Care - Roanoke
Medical Oncology Associates
Fox Valley Hema and Onc SC
Gundersen Lutheran
UNI OF WISCONSIN SCHOOL OF MEDICINE; GI Oncology Research Group, Paul P Carbone Cancer Center
Inst. Alexander Fleming; Oncology Dept
Centro Oncologico Infinito; Oncologia
Hospital Privado de Comunidad; Oncology
Sanatorio Parque de Rosario
ISIS Clinica Especializada
Clínica Viedma
LKH Hohenems; Abteilung für Pulmologie
Tiroler Landeskrankenanstalten Ges.M.B.H.; Innere Medizin Abt. Für Hämatologie & Onkologie
Lkh Natters; Abt. Für Atemwegs- & Lungenkrankheiten
A.Ö. LKH; Abt. für Lungenkrankheiten
Klinikum Wels-Grieskirchen; Lungenabt.
Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Abt. für Onkologie
Krankenhaus Der Stadt Wien Lainz; V. Medizinische Abt.
SMZ - Baumgartner Hohe, Pavilion Leopold; 1.Interne Lungenabteilung, Onkologische Tagesklinik
Clin. Europe (Ste Elisabeth)
Nucleo de Oncologia da Bahia - NOB
Centro de Pesquisa Clínica- Instituto do Câncer do Ceará- ICC
Sociedade beneficente de senhoras Hospital Sirio Libanes
Centro de Estudos e Pesquisas Oncologicas - CESPO
Instituto de Câncer de Brasília
Clinicas Oncologicas Integradas - COI
Hospital de Caridade de Ijui; Oncologia
Clinica de Neoplasias Litoral
Hospital A. C. Camargo; Oncologia
Hospital Sao Jose
Nordsjællands Hospital, Hillerød, Onkologisk Afdeling
Poly Parc Rambot La Provencale; Chimiotherapie Ambulatoire
Centre Francois Baclesse; Oncologie
Centre Hospitalier Intercommunal; Service de Pneumologie
Hopital Nord Ouest;Unite 2c
Centre Oscar Lambret
Hopital Calmette; Pneumologie
Hopital Louis Pradel; Cardiologie B
Hôpital Saint Joseph; Oncologie Medicale
Hopital Nord; Service d'Oncologie Multidisciplinaire et Innovation Thérapeutique
Centre Antoine Lacassagne
Ch Lyon Sud; Chir Onc Gyne Sct Jules Courmont
CH Rene Dubos; Oncologie
Ico Rene Gauducheau; Oncologie
Institut de Cancérologie de Loire
Centre Paul Strauss; Oncologie Medicale
Hia Sainte Anne; Pneumologie
Hopital Sainte Musse; Pneumologie
Clinique Pasteur; Pneumologie
Chi De La Haute Saone De Vesoul; Pneumologie
Zentralklinik Bad Berka GmbH; Pneumologie
Praxis Dr. med. David Borquez
Klinikum Esslingen; Klinik für Kardiologie, Angiologie und Pneumologie
Krankenhaus Nordwest; Klinik f. Onkologie und Hämatologie
SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie
LungenClinic Großhansdorf
Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin I
Universitaetsklinikum des Saarlandes; Innere Medizin V
Fachklinik für Lungenerkrankungen
St. Vincentius Kliniken Karlsruhe; Abteilung Hämatologie / Onkologie
Robert-Koch-Klinik; Pneumologie
Praxis Christian Geßner
Johannes-Wesling-Klinikum Minden; Onkologische Ambulanz / Tagesklinik
Ludwig-Maximilians Uni Klinik Innenstadt; Medizinische Klinik
Pius-Hospital; Klinik fuer Haematologie und Onkologie
Sotiria Hospital
Metropolitan Hospital; 2Nd Oncology Clinic
General Hospital of Thessaloniki Papanikolaou; Uni Pneumonology Dept.
Diavalkaniko Hospital
Citta Ospedaliera; Divisione Oncologia Medica
IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A
Policlinico Universitario Campus Biomedico; Uoc Oncologia Medica
Azienda Ospedaliera San Camillo Forlanini; U.O.C. Pneumologia Ad Indirizzo Oncologico 1
IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A
Az. Osp. Di Busto P.O. Di Saronno; U.O. Di Oncologia Medica
A.O. Universitaria Pisana-Ospedale Cisanello; Dipartimento Cardio Toracico-Pneumologia Ii
Aichi Cancer Center Hospital; Respiratory Medicine
National Cancer Center Hospital East; Thoracic Oncology
National Hospital Organization Shikoku Cancer Center; Thoracic Oncology
National Hospital Organization Kyushu Cancer Center, Thoracic Oncology
Hyogo Cancer Center; Thoracic Oncology
Kanagawa Cardiovascular and Respiratory Center; Respiratory Medicine
Yokohama Municipal Citizen'S Hospital; Respiratory
Miyagi Cancer Center; Respiratory Medicine
Okayama University Hospital; Respiratory and Allergy Medicine
OSAKA CITY GENERAL HOSPITAL;Medical Oncology
Osaka International Cancer Institute; Thoracic Oncology
Shizuoka Cancer Center; Thoracic Oncology
National Cancer Center Hospital; Thoracic Medical Oncology
The Cancer Institute Hospital of JFCR, Respiratory Medicine
American University of Beirut - Medical Center
Hotel Dieu de France; Oncology
Middle East Inst. of Health; Oncology
Centenario Hospital Miguel Hidalgo
Hospital Central Sur de Alta Especialidad Petróleos Mexicanos
Centro Médico Abc the American British Cowdray Medical Center, I.A.P. - Centro de Cáncer
Amphia Ziekenhuis; Afdeling Longziekten
Leyenburg Hospital; Pulmonology
Catharina Ziekenhuis; Dept of Lung Diseases
Ziekenhuis St Jansdal; Dept of Lung Diseases
Academisch Ziekenhuis Maastricht
Antonius Ziekenhuis; Dept of Lung Diseases
College of Medicine & Sciences, Sultan Qaboos University Hospital
Fnsp Fdr Banska Bystrica; Dep of Pneumology&Ftizeology
FNsP Bratislava, Nemocnica Ruzinov
Vychodoslovensky onkologicky ustav
Inst. of Tb & Respiratory Diseases; Dep. of Oncology
Hospital de Cruces; Servicio de Oncologia
Hospital General Univ. de Alicante; Servicio de Oncologia
Centro Oncologico MD Anderson International Espana
Hospital Universitario Clínico San Carlos; Servicio de Oncologia
Hospital Universitario La Paz; Servicio de Oncologia
Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
Hospital Universitario Dr. Peset; Servicio de Oncologia
Hospital Universitario Miguel Servet; Servicio Oncologia
Tawam Hospital; Medical Oncology Department

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Bevacizumab + Standard of Care

Standard of Care

Arm Description

Participants will receive bevacizumab on Day 1 of every 21-days cycle along with standard of care (Erlotinib or Docetaxel or Pemetrexed) as second line treatment, until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).

Participants will receive investigator's choice of standard of care (Erlotinib or Docetaxel or Pemetrexed) according to local practice until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT01351415

First Posted

May 9, 2011

Last Updated

August 17, 2017

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT01351415

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2017

Overall Recruitment Status

Completed

Study Start Date

June 25, 2011 (Actual)

Primary Completion Date

June 25, 2016 (Actual)

Study Completion Date

June 25, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-Squamous Non-Small Cell Lung Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

485 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Bevacizumab + Standard of Care

Arm Type

Experimental

Arm Description

Arm Title

Standard of Care

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Bevacizumab

Other Intervention Name(s)

Avastin

Intervention Description

Participants will receive bevacizumab 7.5 or 15 milligrams per kilogram (mg/kg) intravenously.

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Intervention Description

Docetaxel 60 or 75 milligram per meter square (mg/m^2) on Day 1 every 21 days.

Intervention Type

Drug

Intervention Name(s)

Erlotinib

Intervention Description

Erlotinib 150 mg daily taken on an empty stomach at least one hour before or two hours after the ingestion of food.

Intervention Type

Drug

Intervention Name(s)

Pemetrexed

Intervention Description

Pemetrexed 500 mg/m^2 IV over 10 minutes on Day 1 every 21 days.

Primary Outcome Measure Information:

Title

Overall Survival (OS)

Description

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.

Time Frame