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

Non Small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01221077
• Other study ID #: OSI-906-207
• Status: Completed
• Phase: Phase 2
• Start date: April 8, 2011
• Est. completion date: September 1, 2014

Study information

• Verified date: January 2019
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: September 1, 2014
• Est. primary completion date: March 1, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• OSI-906
As of 01 March 2013, OSI-906 is no longer being administered
• Erlotinib
Erlotinib administered orally
• Placebo
As of 01 March 2013, the matching placebo is no longer being administered

Locations

Country	Name	City	State
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
Hong Kong	Pamela Youde Nethersole Eastern Hospital	Chai Wan
Korea, Republic of	Chonnam National University Hwasun Hospital	Ilsimri	Hwasun-gun
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Asan Medical Center	Songpa-gu	Seoul
Singapore	Johns Hopkins Singapore International Medical Centre	Singapore
Singapore	Oncocare Cancer Center	Singapore
Thailand	Maharaj Nakorn Chiangmai	Chiang Mai
Thailand	Khon Kaen University	Khon Kaen
Thailand	National Cancer Institute	Phayathai	Bangkok
Thailand	Songklanagarind Hospital, Prince of Songkla University	Songkla
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	University of California, San Diego/Moores Cancer Center	La Jolla	California
United States	University of Tennessee Cancer Institute	Memphis	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Seattle Cancer Care Alliance University of Washington	Seattle	Washington
United States	Swedish Cancer Institute	Seattle	Washington
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Cleveland Clinic Florida	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Inc

Countries where clinical trial is conducted

United States,  Canada,  Hong Kong,  Korea, Republic of,  Singapore,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival (OS)	Time from the date of randomization until the documented date of death.	33 months
Secondary	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
Secondary	Best Overall Response Rate		33 months
Secondary	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
Secondary	Safety assessed through evaluation of adverse events, laboratory, physical examination, and Electrocardiogram (ECG) data		33 months

External Links

•   Link to results on the Astellas Clinical Study Results website