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).

Non-Squamous Non-Small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00760929
• Other study ID #: NO21160
• Secondary ID: 2008-001736-12
• Status: Terminated
• Phase: Phase 2
• Start date: November 10, 2008
• Est. completion date: June 25, 2010

Study information

• Verified date: December 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 171
• Est. completion date: June 25, 2010
• Est. primary completion date: June 25, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Placebo
iv 9mg/kg weekly
• Placebo
iv 16mg/kg every 3 weeks
• RG1507
iv 9mg/kg weekly
• RG1507
iv 16mg/kg every 3 weeks
• erlotinib [Tarceva]
150mg oral daily

Locations

Country	Name	City	State
Australia	Flinders Medical Center; Medical Oncology	Adelaide	South Australia
Australia	Frankston Hospital; Oncology/Haematology	Frankston	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	GHdC Site Notre Dame	Charleroi
Belgium	UZ Antwerpen	Edegem
Belgium	UZ Leuven Gasthuisberg	Leuven
Belgium	Chr de La Citadelle	Liege
Canada	Lakeridge Health Oshawa; Oncology	Oshawa	Ontario
France	Hopital Albert Michallon; Medecine Aigue Specialisee Pneumologie	La Tronche
France	Hopital de La Croix Rousse; Service de Pneumologie	Lyon
France	Fondation Hopital Saint Joseph; Pole Cancerologie, Imagerie Medicale Service d'Oncologie	Paris
France	Hopital Tenon;Pneumologie	Paris
France	Hopital Larrey; Clinique Des Voies Respiratoires	Toulouse
Germany	Zentralklinik Bad Berka GmbH; Pneumologie	Bad Berka
Germany	Helios Klinikum Emil von Behring GmbH	Berlin
Germany	LungenClinic Großhansdorf GmbH	Großhansdorf
Germany	Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin I	Halle (Saale)
Germany	Asklepios Klinik Harburg; Thoraxzentrum	Hamburg
Germany	Thoraxklinik Heidelberg gGmbH	Heidelberg
Germany	Stiftung Kathol. Krankenhaus Marienhospital Herne Klinik Mitte Frauenklinik	Herne
Germany	Klinikum Leverkusen; Med. Klinik III / Onkologie	Leverkusen
Germany	Ludwig-Maximilians Uni Klinik Innenstadt; Medizinische Klinik	Muenchen
Ireland	St. James Hospital; Oncology	Dublin
Italy	IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A	Genova	Liguria
Italy	Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia	Milano	Lombardia
Italy	Az. Osp. S. Luigi Gonzaga; Malattie Apparato Respiratorio 5 Ad Indirizzo Oncologico	Orbassano	Piemonte
Italy	Arcispedale Santa Maria Nuova; Oncologia	Reggio Emilia	Emilia-Romagna
Italy	Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica	Sant'Andrea Delle Fratte (PG)	Umbria
Poland	Medical University of Gdansk	Gdansk
Poland	SK Przemienienia Panskiego UM im.K.Marcinkowskiego	Poznan
Poland	Specjalistyczny Szpital Im. Prof. A. Sokolowskiego; Oddziall Chemioterapii	Szczecin
Poland	Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii	Warszawa
Spain	Hospital Clínic i Provincial; Servicio de Hematología y Oncología	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia	Barcelona
Spain	Hospital de Cruces; Servicio de Oncologia	Bilbao	Vizcaya
Spain	Hospital Universitario Puerta de Hierro; Servicio de Oncologia	Majadahonda	Madrid
Spain	Hospital Regional Universitario Carlos Haya; Servicio de Oncologia	Malaga
United Kingdom	Royal Surrey County Hospital; St. Lukes Cancer Centre	Guildford
United Kingdom	Wythenshawe Hospital; North West Lung Centre	Manchester
United Kingdom	Sir Bobby Robson Cancer Research Centre	Newcastle Upon Tyne
United Kingdom	New Cross Hospital; Deansley Centre	Wolverhampton
United States	Emory Univ Winship Cancer Inst	Atlanta	Georgia
United States	Tower Cancer Research Foundation	Beverly Hills	California
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	Chattanooga Oncology and Hematology Associates, PC	Chattanooga	Tennessee
United States	University of Chicago Medical Center; Dept. of Medicine/Section of Nephrology	Chicago	Illinois
United States	North Shore University Health System	Glenview	Illinois
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Carolina Oncology Specialists, PA - Hickory	Hickory	North Carolina
United States	Joliet Oncology Hematology Associates, Ltd.	Joliet	Illinois
United States	Sarah Cannon Research Inst.	Nashville	Tennessee
United States	Florida Cancer Inst.	New Port Richey	Florida
United States	Virginia Cancer Institute	Richmond	Virginia
United States	St. Joseph Medical Center	Towson	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Ireland,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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