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).

A Randomized, Placebo Controlled Study to Determine the Effect of Two Dose Schedules of R1507 or Placebo, Both in Combination With Erlotinib (Tarceva®), on Progression-free Survival in Patients With Advanced Non-small Cell Lung Cancer With Disease Progression After First or Second Line Chemotherapy

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.

Study Overview

• Status: Terminated
• Conditions: Non-Squamous Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: RG1507; Drug: erlotinib [Tarceva]; Drug: Placebo; Drug: Placebo; Drug: RG1507

• Study Type: Interventional
• Enrollment (Actual): 171
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5041
      • Flinders Medical Center; Medical Oncology
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Frankston Hospital; Oncology/Haematology
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Charleroi, Belgium, 6000
    • GHdC Site Notre Dame
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
  • Liege, Belgium, 3500
    • CHR de la Citadelle
• Canada
  • Ontario
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health Oshawa; Oncology
• France
  • La Tronche, France, 38700
    • Hopital Albert Michallon; Medecine Aigue Specialisee Pneumologie
  • Lyon, France, 69317
    • Hopital de La Croix Rousse; Service de Pneumologie
  • Paris, France, 75970
    • Hopital Tenon;Pneumologie
  • Paris, France, 75674
    • Fondation Hopital Saint Joseph; Pole Cancerologie, Imagerie Medicale Service d'Oncologie
  • Toulouse, France, 31400
    • Hopital Larrey; Clinique Des Voies Respiratoires
• Germany
  • Bad Berka, Germany, 99437
    • Zentralklinik Bad Berka GmbH; Pneumologie
  • Berlin, Germany, 14165
    • Helios Klinikum Emil von Behring GmbH
  • Großhansdorf, Germany, 22927
    • LungenClinic Großhansdorf GmbH
  • Halle (Saale), Germany, 06120
    • Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin I
  • Hamburg, Germany, 21075
    • Asklepios Klinik Harburg; Thoraxzentrum
  • Heidelberg, Germany, 69126
    • Thoraxklinik Heidelberg gGmbH
  • Herne, Germany, 44625
    • Stiftung Kathol. Krankenhaus Marienhospital Herne Klinik Mitte Frauenklinik
  • Leverkusen, Germany, 51375
    • Klinikum Leverkusen; Med. Klinik III / Onkologie
  • Muenchen, Germany, 80336
    • Ludwig-Maximilians Uni Klinik Innenstadt; Medizinische Klinik
• Ireland
  • Dublin, Ireland, 8
    • St. James Hospital; Oncology
• Italy
  • Emilia-Romagna
    • Reggio Emilia, Emilia-Romagna, Italy, 42100
      • Arcispedale Santa Maria Nuova; Oncologia
  • Liguria
    • Genova, Liguria, Italy, 16132
      • IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A
  • Lombardia
    • Milano, Lombardia, Italy, 20162
      • Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
  • Piemonte
    • Orbassano, Piemonte, Italy, 10043
      • Az. Osp. S. Luigi Gonzaga; Malattie Apparato Respiratorio 5 Ad Indirizzo Oncologico
  • Umbria
    • Sant'Andrea Delle Fratte (PG), Umbria, Italy, 06132
      • Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica
• Poland
  • Gdansk, Poland, 80-952
    • Medical University of Gdansk
  • Poznan, Poland, 60-569
    • SK Przemienienia Panskiego UM im.K.Marcinkowskiego
  • Szczecin, Poland, 70-891
    • Specjalistyczny Szpital Im. Prof. A. Sokolowskiego; Oddziall Chemioterapii
  • Warszawa, Poland, 02-781
    • Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial; Servicio de Hematología y Oncología
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia
  • Malaga, Spain, 29010
    • Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro; Servicio de Oncologia
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48903
      • Hospital de Cruces; Servicio de Oncologia
• United Kingdom
  • Guildford, United Kingdom, GU2 7XX
    • Royal Surrey County Hospital; St. Lukes Cancer Centre
  • Manchester, United Kingdom, M23 9LT
    • Wythenshawe Hospital; North West Lung Centre
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Sir Bobby Robson Cancer Research Centre
  • Wolverhampton, United Kingdom, WV10 0QP
    • New Cross Hospital; Deansley Centre
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Tower Cancer Research Foundation
  • Florida
    • New Port Richey, Florida, United States, 34655
      • Florida Cancer Inst.
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Univ Winship Cancer Inst
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center; Dept. of Medicine/Section of Nephrology
    • Glenview, Illinois, United States, 60026
      • North Shore University Health System
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology Hematology Associates, Ltd.
  • Maryland
    • Towson, Maryland, United States, 21204
      • St. Joseph Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Inst.
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital.
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • North Carolina
    • Hickory, North Carolina, United States, 28602
      • Carolina Oncology Specialists, PA - Hickory
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Oncology and Hematology Associates, PC
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Inst.
  • Virginia
    • Richmond, Virginia, United States, 23226
      • Virginia Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo for R1507 (16mg/kg iv)	Drug: erlotinib [Tarceva]; 150mg oral daily; Drug: Placebo; iv 9mg/kg weekly; Drug: Placebo; iv 16mg/kg every 3 weeks
Placebo Comparator: Placebo for R1507 (9mg/kg iv)	Drug: erlotinib [Tarceva]; 150mg oral daily; Drug: Placebo; iv 9mg/kg weekly; Drug: Placebo; iv 16mg/kg every 3 weeks
Experimental: R1507 (16mg/kg iv)	Drug: RG1507; iv 9mg/kg weekly; Drug: erlotinib [Tarceva]; 150mg oral daily; Drug: RG1507; iv 16mg/kg every 3 weeks
Experimental: R1507 (9mg/kg iv)	Drug: RG1507; iv 9mg/kg weekly; Drug: erlotinib [Tarceva]; 150mg oral daily; Drug: RG1507; iv 16mg/kg every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Progression Free Survival (PFS)	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.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	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.	From baseline up to 20 months
Objective Response Rate	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.	From baseline up to 20 months
Duration of Response	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.	From baseline up to 20 months
Time to Response	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).	From baseline up to 20 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Ramalingam SS, Spigel DR, Chen D, Steins MB, Engelman JA, Schneider CP, Novello S, Eberhardt WE, Crino L, Habben K, Liu L, Janne PA, Brownstein CM, Reck M. Randomized phase II study of erlotinib in combination with placebo or R1507, a monoclonal antibody to insulin-like growth factor-1 receptor, for advanced-stage non-small-cell lung cancer. J Clin Oncol. 2011 Dec 1;29(34):4574-80. doi: 10.1200/JCO.2011.36.6799. Epub 2011 Oct 24.

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2008
• Primary Completion (Actual): June 25, 2010
• Study Completion (Actual): June 25, 2010

Study Registration Dates

• First Submitted: September 25, 2008
• First Submitted That Met QC Criteria: September 25, 2008
• First Posted (Estimate): September 26, 2008

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: December 5, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Protein Kinase Inhibitors; Erlotinib Hydrochloride; Antibodies, Monoclonal
• Other Study ID Numbers: NO21160; 2008-001736-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).