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A Study of the Effect of R1507 in Combination With Tarceva (Erlotinib) on Progression-Free Survival in Patients With Stage IIIb/IV Non-Small Cell Lung Cancer (NSCLC).

Phase 2
Terminated
Conditions
Non-Squamous Non-Small Cell Lung Cancer
Interventions
Drug: RG1507
Drug: Placebo
Drug: erlotinib [Tarceva]
Registration Number
NCT00760929
Lead Sponsor
Hoffmann-La Roche
Brief Summary

This 4 arm study in patients with advanced Stage IIIb/IV non-small cell cancer (NSCLC) who failed at least one standard chemotherapy regimen will determine the proportion of patients with progression-free survival at 12 weeks following combination therapy with R1507 and Tarceva or placebo and Tarceva. Patients will be randomized to one of four treatment arms to receive R1507 (9mg/kg iv) or placebo weekly or R1507 (16mg/kg iv) or placebo every 3 weeks. Tarceva (150mg oral daily) will be administered in all treatment arms. Other disease-related endpoints including overall survival, objective response rate, time to response, time to progressive disease and duration of response will also be evaluated. The anticipated time on study treatment is 1-2 years, and the target sample size is \<500 individuals.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
171
Inclusion Criteria
  • male or female patients >=18 years with histologically documented inoperable, locally advanced or metastatic (stage IIIB or IV) NSCLC;
  • patients must have failed at least one but no more than two standard chemotherapy regimens;
  • measurable disease according to the RECIST criteria;
  • Eastern Cooperative Oncology Group (ECOG) performance status;
  • life expectancy >12 weeks.
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Exclusion Criteria
  • patients with active central nervous system (CNS) lesions;
  • prior treatment with agents acting via insulin-like growth factor 1 receptor (IGF-1R) inhibition or epidermal growth factor receptor (EGFR) targeting;
  • administration with high doses of systemic corticosteroids;
  • radiotherapy in the 4 weeks prior to study start;
  • surgery or significant traumatic injury with in the last 2 weeks prior to study start.
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
R1507 (16mg/kg iv)RG1507-
Placebo for R1507 (16mg/kg iv)Placebo-
Placebo for R1507 (16mg/kg iv)erlotinib [Tarceva]-
Placebo for R1507 (9mg/kg iv)Placebo-
Placebo for R1507 (9mg/kg iv)erlotinib [Tarceva]-
R1507 (16mg/kg iv)erlotinib [Tarceva]-
R1507 (9mg/kg iv)RG1507-
R1507 (9mg/kg iv)erlotinib [Tarceva]-
Primary Outcome Measures
NameTimeMethod
Number of Participants With Progression Free Survival (PFS)12 weeks

PFS was defined as the time at which half of the participants have progressed (progressive disease \[PD\]) based on RECIST tumor response criteria or died from any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Participants who had not died or progressed at the time of the final analysis were censored at the date of last contact.

Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS)From baseline up to 20 months

OS was defined as the median time, in weeks, from the date of randomization to the date of death, due to any cause. Participants who have not died at the time of the final analysis will be censored at the date the participant was last known to be alive. The 90% CI was estimated using Kaplan-Meier methodology.

Objective Response RateFrom baseline up to 20 months

Objective response rate (ORR) was defined by RECIST criteria as the best response achieved by a patient over the course of the trial, which includes a complete response (CR) or partial response (PR) that has been confirmed by a second tumor assessment no earlier than 4 weeks after the initial documentation, stable disease (SD), or progressive disease (PD). PR was defined as ≥ 30% decrease in sum of longest diameter of all target lesions, from baseline sum. CR was defined as disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. PD = 20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions. SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on the study.

Time to ResponseFrom baseline up to 20 months

This is defined for participants with objective response, as the date of randomization to the date of first CR or PR which will be the date the response is first radiographically documented following initiation of therapy (the date of the actual imaging modality).

Duration of ResponseFrom baseline up to 20 months

Duration of response was defined as the time from the first documented complete response (CR) or partial response (PR) to the first documented disease progression (PD) or death, whichever occurs first. A CR was defined as the disappearance of all target lesions (TL). A PR was defined as at least a 30% decrease in the sum of the longest diameter (SLD) of TLs taking as reference the Baseline SLD. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since treatment started or the unequivocal progression of existing non-TLs.

Trial Locations

Locations (57)

Hackensack University Medical Center

🇺🇸

Hackensack, New Jersey, United States

Lakeridge Health Oshawa; Oncology

🇨🇦

Oshawa, Ontario, Canada

North Shore University Health System

🇺🇸

Glenview, Illinois, United States

University of Chicago Medical Center; Dept. of Medicine/Section of Nephrology

🇺🇸

Chicago, Illinois, United States

St. James Hospital; Oncology

🇮🇪

Dublin, Ireland

SK Przemienienia Panskiego UM im.K.Marcinkowskiego

🇵🇱

Poznan, Poland

Florida Cancer Inst.

🇺🇸

New Port Richey, Florida, United States

Hospital de Cruces; Servicio de Oncologia

🇪🇸

Bilbao, Vizcaya, Spain

LungenClinic Großhansdorf GmbH

🇩🇪

Großhansdorf, Germany

Ludwig-Maximilians Uni Klinik Innenstadt; Medizinische Klinik

🇩🇪

Muenchen, Germany

Sir Bobby Robson Cancer Research Centre

🇬🇧

Newcastle Upon Tyne, United Kingdom

Emory Univ Winship Cancer Inst

🇺🇸

Atlanta, Georgia, United States

Stiftung Kathol. Krankenhaus Marienhospital Herne Klinik Mitte Frauenklinik

🇩🇪

Herne, Germany

Tower Cancer Research Foundation

🇺🇸

Beverly Hills, California, United States

Medical University of Gdansk

🇵🇱

Gdansk, Poland

Cliniques Universitaires St-Luc

🇧🇪

Bruxelles, Belgium

Joliet Oncology Hematology Associates, Ltd.

🇺🇸

Joliet, Illinois, United States

Hospital Universitario Puerta de Hierro; Servicio de Oncologia

🇪🇸

Majadahonda, Madrid, Spain

Royal Surrey County Hospital; St. Lukes Cancer Centre

🇬🇧

Guildford, United Kingdom

Chr de La Citadelle

🇧🇪

Liege, Belgium

Arcispedale Santa Maria Nuova; Oncologia

🇮🇹

Reggio Emilia, Emilia-Romagna, Italy

Wythenshawe Hospital; North West Lung Centre

🇬🇧

Manchester, United Kingdom

Specjalistyczny Szpital Im. Prof. A. Sokolowskiego; Oddziall Chemioterapii

🇵🇱

Szczecin, Poland

Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii

🇵🇱

Warszawa, Poland

Thoraxklinik Heidelberg gGmbH

🇩🇪

Heidelberg, Germany

IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A

🇮🇹

Genova, Liguria, Italy

Hospital Clínic i Provincial; Servicio de Hematología y Oncología

🇪🇸

Barcelona, Spain

Hospital Regional Universitario Carlos Haya; Servicio de Oncologia

🇪🇸

Malaga, Spain

New Cross Hospital; Deansley Centre

🇬🇧

Wolverhampton, United Kingdom

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

🇮🇹

Orbassano, Piemonte, Italy

Klinikum Leverkusen; Med. Klinik III / Onkologie

🇩🇪

Leverkusen, Germany

Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia

🇪🇸

Barcelona, Spain

Dana Farber Cancer Inst.

🇺🇸

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

GHdC Site Notre Dame

🇧🇪

Charleroi, Belgium

Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica

🇮🇹

Sant'Andrea Delle Fratte (PG), Umbria, Italy

Hopital Tenon;Pneumologie

🇫🇷

Paris, France

Hopital Larrey; Clinique Des Voies Respiratoires

🇫🇷

Toulouse, France

Sarah Cannon Research Inst.

🇺🇸

Nashville, Tennessee, United States

Massachusetts General Hospital.

🇺🇸

Boston, Massachusetts, United States

St. Joseph Medical Center

🇺🇸

Towson, Maryland, United States

Carolina Oncology Specialists, PA - Hickory

🇺🇸

Hickory, North Carolina, United States

Virginia Cancer Institute

🇺🇸

Richmond, Virginia, United States

Chattanooga Oncology and Hematology Associates, PC

🇺🇸

Chattanooga, Tennessee, United States

Flinders Medical Center; Medical Oncology

🇦🇺

Adelaide, South Australia, Australia

UZ Leuven Gasthuisberg

🇧🇪

Leuven, Belgium

Frankston Hospital; Oncology/Haematology

🇦🇺

Frankston, Victoria, Australia

Sir Charles Gairdner Hospital

🇦🇺

Nedlands, Western Australia, Australia

UZ Antwerpen

🇧🇪

Edegem, Belgium

Hopital de La Croix Rousse; Service de Pneumologie

🇫🇷

Lyon, France

Fondation Hopital Saint Joseph; Pole Cancerologie, Imagerie Medicale Service d'Oncologie

🇫🇷

Paris, France

Hopital Albert Michallon; Medecine Aigue Specialisee Pneumologie

🇫🇷

La Tronche, France

Zentralklinik Bad Berka GmbH; Pneumologie

🇩🇪

Bad Berka, Germany

Helios Klinikum Emil von Behring GmbH

🇩🇪

Berlin, Germany

Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin I

🇩🇪

Halle (Saale), Germany

Asklepios Klinik Harburg; Thoraxzentrum

🇩🇪

Hamburg, Germany

Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia

🇮🇹

Milano, Lombardia, Italy

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