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

NCT01221077 | Completed Phase 2 DMC

• 1 other identifier: OSI-906-207
• Study Type: interventional
• Target: 88
• Locations: 6 countries
• Sites: 29

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.

Conditions

NSCLC; Non Small Cell Lung Cancer

Keywords

NSCLC; Epidermal Growth Factor Receptor; EGFR; Non-small cell lung cancer; Tarceva; Activating mutations; OSI-906; Chemonaive; IGF-IR; Erlotinib

Outcome Measures

Primary Outcomes (1)

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

  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.

  15 months

Secondary Outcomes (5)

• Overall Survival (OS)

  33 months

• Disease Control Rate (DCR)

  33 months

• Best Overall Response Rate

  33 months

• Duration of Response (CR/PR)

  33 months

• Safety assessed through evaluation of adverse events, laboratory, physical examination, and Electrocardiogram (ECG) data

  33 months

Study Arms (2)

Arm A: Erlotinib plus OSI-906

EXPERIMENTAL

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

Drug: OSI-906; Drug: Erlotinib

Arm B: Erlotinib plus Placebo

PLACEBO COMPARATOR

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

Drug: Erlotinib; Drug: Placebo

Interventions

OSI-906 DRUG

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

Arm A: Erlotinib plus OSI-906

Erlotinib DRUG

Erlotinib administered orally

Also known as: OSI-774, Tarceva

Arm A: Erlotinib plus OSI-906; Arm B: Erlotinib plus Placebo

Placebo DRUG

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

Arm B: Erlotinib plus Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Serum creatinine \<= 1.5 x Upper Limit of Normal (ULN)
• Potassium, magnesium, and calcium within normal limits (supplementation and re-testing is permitted)
• Total bilirubin \<= 1.5 x ULN
• AST and ALT \<= 2.5 x ULN, or \<= 5 x ULN if patient has documented liver metastases
• Female subject must be either:

You may not qualify if:

• 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
• Mean QTcF interval \>= 450 msec at screening
• Use of drugs that have a known risk of causing Torsades de Pointes (TdP) ('Torsades List' on www.azcert.org/medical-pros/drug-lists/bycategory.cfm) are prohibited within 14 days prior to randomization
• Use of strong/moderate CYP1A2 inhibitors such as ciprofloxacin and fluvoxamine. Other less potent CYP1A2 inhibitors/inducers are not excluded
• Use of strong/moderate CYP3A4 inhibitors and inducers
• History of cerebrovascular accident (CVA) within 6 months prior to randomization or that resulted in ongoing neurologic instability

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (29)

University of California, San Diego/Moores Cancer Center

La Jolla, California, 92093, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Tennessee Cancer Institute

Memphis, Tennessee, 31804, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Seattle Cancer Care Alliance University of Washington

Seattle, Washington, 98109, United States

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Pamela Youde Nethersole Eastern Hospital

Chai Wan, 852, Hong Kong

Location

Oncocare Cancer Center

Singapore, 258499, Singapore

Location

Johns Hopkins Singapore International Medical Centre

Singapore, 308433, Singapore

Location

Chonnam National University Hwasun Hospital

Ilsimri, Hwasun-gun, 519809, South Korea

Location

Asan Medical Center

Songpa-gu, Seoul, 138736, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 463-707, South Korea

Location

Samsung Medical Center

Seoul, 135710, South Korea

Location

Korea University Anam Hospital

Seoul, 136705, South Korea

Location

National Cancer Institute

Phayathai, Bangkok, 10400, Thailand

Location

Maharaj Nakorn Chiangmai

Chiang Mai, 50002, Thailand

Location

Khon Kaen University

Khon Kaen, 40002, Thailand

Location

Songklanagarind Hospital, Prince of Songkla University

Songkhla, 90110, Thailand

Location

Related Links

• Link to results on the Astellas Clinical Study Results website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanol; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Medical Director

  Astellas Pharma Global Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2010
• First Posted: October 14, 2010
• Study Start: April 8, 2011
• Primary Completion: March 1, 2013
• Study Completion: September 1, 2014
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

TH (4); HK (1); KR (5); US (13); CA (4); SG (2)