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

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

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.

Study Overview

• Status: Completed
• Conditions: NSCLC; Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: OSI-906; Drug: Erlotinib; Drug: Placebo

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).

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• Hong Kong
  • Chai Wan, Hong Kong, 852
    • Pamela Youde Nethersole Eastern Hospital
• Singapore
  • Singapore, Singapore, 308433
    • Johns Hopkins Singapore International Medical Centre
  • Singapore, Singapore, 258499
    • Oncocare Cancer Center
• South Korea
  • Seongnam-si, South Korea, 463-707
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 135710
    • Samsung Medical Center
  • Seoul, South Korea, 136705
    • Korea University Anam Hospital
  • Hwasun-gun
    • Ilsimri, Hwasun-gun, South Korea, 519809
      • Chonnam National University Hwasun Hospital
  • Seoul
    • Songpa-gu, Seoul, South Korea, 138736
      • Asan Medical Center
• Thailand
  • Chiang Mai, Thailand, 50002
    • Maharaj Nakorn Chiangmai
  • Khon Kaen, Thailand, 40002
    • Khon Kaen University
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital, Prince of Songkla University
  • Bangkok
    • Phayathai, Bangkok, Thailand, 10400
      • National Cancer Institute
• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California, San Diego/Moores Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Memphis, Tennessee, United States, 31804
      • University of Tennessee Cancer Institute
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance University of Washington

Participation Criteria

Eligibility Criteria

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

Description

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
  • 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:

  • Of non child bearing potential:

    1. post-menopausal (defined as at least 1 year without any menses) prior to Screening, or
    2. documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening).

  • Or, if of childbearing potential:

    1. must have a negative urine pregnancy test at Screening, and

    2. must use two forms of birth control (at least one of which must be a barrier method) starting at Screening and throughout the study period and for 30 days after final study drug administration. Acceptable forms include:

       1. Established use of oral, injected or implanted hormonal methods of contraception;
       2. Placement of an intrauterine device (IUD) or intrauterine system (IUS);
       3. Barrier methods of contraception: Condom OR Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
• Female subject must not be breastfeeding at Screening or during the study period and for 30 days after final study drug administration.
• Female subject must not donate ova starting at Screening and throughout the study period and for 30 days after final study drug administration.

• Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at Screening and continue throughout the study period and for 30 days after final study drug administration. Acceptable forms include:

  1. Established use of oral, injected or implanted hormonal methods of contraception.
  2. Placement of an intrauterine device (IUD) or intrauterine system (IUS).
  3. Barrier methods of contraception: Condom OR Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
• Male subjects must not donate sperm starting at Screening and throughout the study period and for at least 30 days after final study drug administration.
• Patients must provide written informed consent to participate in the study
• Patients may not have received chemotherapy for advanced NSCLC. Previous adjuvant and/or neoadjuvant treatment for NSCLC is permitted
• Prior radiation therapy is permitted provided patients have recovered from the acute, toxic effects of radiotherapy prior to randomization. A minimum of 28 days must have elapsed between the end of radiotherapy and randomization
• Prior surgery is permitted provided that the surgery was done >= 28 days prior to randomization and adequate wound healing has occurred prior to randomization

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
• 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
• History of any psychiatric or neurologic condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent
• Pregnant or breast-feeding females
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drug
• Active infection, serious underlying medical condition (including any type of active seizure disorder within 12 months prior to randomization), symptomatic brain metastases, or serious chronic illness that would impair the ability of the patient to receive study drug

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Erlotinib plus OSI-906; As of 01 March 2013, OSI-906 is no longer being administered	Drug: OSI-906; As of 01 March 2013, OSI-906 is no longer being administered; Drug: Erlotinib; Erlotinib administered orally; Other Names: Tarceva; OSI-774
Placebo Comparator: Arm B: Erlotinib plus Placebo; As of 01 March 2013, the matching placebo is no longer being administered	Drug: Erlotinib; Erlotinib administered orally; Other Names: Tarceva; OSI-774; Drug: Placebo; As of 01 March 2013, the matching placebo is no longer being administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from the date of randomization until the documented date of death.	33 months
Disease Control Rate (DCR)	Proportion of patients with a best overall response of complete response (CR), partial response (PR), or stable disease based on RECIST version 1.1 criteria.	33 months
Best Overall Response Rate		33 months
Duration of Response (CR/PR)	Time from the date of the first documented response (CR/PR) to documented progression or death due to underlying cancer. Defined for patients whose best overall response was CR or PR.	33 months
Safety assessed through evaluation of adverse events, laboratory, physical examination, and Electrocardiogram (ECG) data		33 months

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Medical Director, Astellas Pharma Global Development

Publications and helpful links

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2011
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: October 5, 2010
• First Submitted That Met QC Criteria: October 13, 2010
• First Posted (Estimated): October 14, 2010

Study Record Updates

• Last Update Posted (Estimated): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 13, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; Non-small cell lung cancer; EGFR; Erlotinib; Tarceva; Epidermal Growth Factor Receptor; OSI-906; Chemonaive; Activating mutations; IGF-IR
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinazolines; Erlotinib Hydrochloride; 3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanol
• Other Study ID Numbers: OSI-906-207

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR