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 2TerminatedNCT00760929

Hoffmann-La Roche171 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

171

Conditions

Non-Squamous Non-Small Cell Lung Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (57)

Tower Cancer Research Foundation

Beverly Hills, California, United States

Florida Cancer Inst.

New Port Richey, Florida, United States

Emory Univ Winship Cancer Inst

Atlanta, Georgia, 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

Outcomes

Primary Outcomes

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.

Time frame: 12 weeks

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: From baseline up to 20 months