Clinical Trials/NCT01221077

NCT01221077

Completed

Phase 2

A Randomized, Double-Blind, Phase 2 Study of Erlotinib (Tarceva®) in Combination With OSI-906 or Placebo in Chemonaive Patients With Advanced NSCLC With Activating Mutations of the Epidermal Growth Factor Receptor (EGFR) Gene

Astellas Pharma Inc29 sites in 6 countries88 target enrollmentApril 8, 2011

ConditionsNSCLC Non Small Cell Lung Cancer

InterventionsPlacebo OSI-906 Erlotinib

DrugsOSI-906 Erlotinib Placebo

Overview

Phase: Phase 2
Intervention: Placebo
Conditions: NSCLC
Sponsor: Astellas Pharma Inc
Enrollment: 88
Locations: 29
Primary Endpoint: Progression-free survival of OSI-906 in combination with Erlotinib or Erlotinib plus placebo
Status: Completed
Last Updated: 5 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

A multicenter, randomized, double-blind, placebo-controlled, phase 2 study of Erlotinib (Tarceva®) in combination with OSI-906 in Patients with Advanced non-small cell lung cancer (NSCLC) with Activating Mutations of the Epidermal Growth Factor Receptor (EGFR) Gene who are Chemonaive.

Detailed Description

Based on the recommendation of the Data Monitoring Committee, OSI-906 and matching placebo are no longer being administered as of 01 March 2013. This is a multi-center, randomized (1:1), double-blind, placebo-controlled, phase 2 study. Patients will be stratified according to the following 2 parameters: (1) EGFR activating mutation type (exon 19 deletion versus exon 21 single point mutation); and (2) Eastern Cooperative Oncology Group (ECOG) performance status (0 vs. 1).

Registry

clinicaltrials.gov

Start Date

April 8, 2011

End Date

September 1, 2014

Last Updated

5 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Astellas Pharma Inc

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Historically confirmed advanced NSCLC stages IIIB or IV
•Exon 19 deletion or exon 21 activating mutation in EGFR
•EGFR mutation status must be confirmed for participation in the study. EGFR can be performed either by central or local laboratory. If analysis is done locally, verifiable documentation confirming the EGFR mutation status must be submitted for review and approval by sponsor prior to randomization. If no local result is available, formalin-fixed, paraffin-embedded archival tissue representative of the tumor or, in the absence of archival tissue, a fresh tumor tissue sample of sufficient size to perform EGFR mutation analysis must be submitted centrally. Results of the central analysis must be available prior to randomization. Additionally, subjects should provide tissue blocks for biomarker central analysis whenever possible. Ideal tissue requirement: block with ≥5 mm2 tumor area sufficient to provide four 4-micron, and five 10-micron sections
•Measurable disease according to RECIST (version 1.1)
•ECOG performance status 0-1
•Must be able to take oral medication
•Fasting glucose \<= 150 mg/dL (8.3 mmol/L). Concurrent use of non-insulinotropic anti hyperglycemic therapy is permitted if the dose has been stable for \>= 4 weeks at the time of randomization
•Adequate hematopoietic, hepatic, and renal function as follows:
•Neutrophil count \>= 1500/uL
•Platelet count \>= 100,000/uL

Exclusion Criteria

•Prior exposure to agents directed at the Human Epidermal Receptor (HER) axis (eg, erlotinib, gefitinib, and cetuximab)
•Prior insulin-like growth factor -1 receptor (IGF-1R) inhibitor therapy
•Malignancies other than NSCLC within the past 3 years (exceptions if curatively treated; basal or squamous cell carcinoma of skin; locally advanced prostate cancer; ductal carcinoma in situ of breast; in situ cervical carcinoma; and superficial bladder cancer)
•Diabetes mellitus currently requiring insulinotropic or insulin therapy
•Use of proton pump inhibitors such as omeprazole within 14 days prior to randomization. H2-receptor antagonists such as ranitidine are not excluded
•Symptomatic brain metastases that are not stable, require steroids, or have required radiation and/or other related treatment (i.e., anti-epileptic medication) within 21 days prior to randomization
•Participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half lives whichever is longer, prior to the initiation of Screening or during the course of the study.
•History of poorly controlled gastrointestinal disorders that could affect the absorption of study drug (eg, Crohn's disease or ulcerative colitis)
•History (within last 6 months) of significant cardiovascular disease unless the disease is well-controlled. Significant cardiac disease includes second/third degree heart block; clinically significant ischemic heart disease; superior vena cava (SVC) syndrome; poorly controlled hypertension; congestive heart failure of New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but no ordinary physical activity results in fatigue, palpitation, or dyspnea)
•History of arrhythmia (multifocal premature ventricular contractions \[PVCs\], bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is symptomatic or requires treatment (\>= grade 3), left bundle branch block (LBBB), or asymptomatic sustained ventricular tachycardia are not allowed. Patients with atrial fibrillation controlled by medication are not excluded

Arms & Interventions

Arm B: Erlotinib plus Placebo

As of 01 March 2013, the matching placebo is no longer being administered

Intervention: Placebo

Arm A: Erlotinib plus OSI-906

As of 01 March 2013, OSI-906 is no longer being administered

Intervention: OSI-906

Arm A: Erlotinib plus OSI-906

As of 01 March 2013, OSI-906 is no longer being administered

Intervention: Erlotinib

Arm B: Erlotinib plus Placebo

As of 01 March 2013, the matching placebo is no longer being administered

Intervention: Erlotinib

Outcomes

Primary Outcomes

Progression-free survival of OSI-906 in combination with Erlotinib or Erlotinib plus placebo

Time Frame: 15 months

Time from randomization to disease progression based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by investigator or death due to any cause, whichever occurs first.

Secondary Outcomes

Best Overall Response Rate(33 months)
Duration of Response (CR/PR)(33 months)
Overall Survival (OS)(33 months)
Disease Control Rate (DCR)(33 months)
Safety assessed through evaluation of adverse events, laboratory, physical examination, and Electrocardiogram (ECG) data(33 months)