Phase 2 Study of Maintenance OSI-906 Plus Erlotinib (Tarceva®), or Placebo Plus Erlotinib in Patients With Nonprogression Following 4 Cycles of Platinum-based Chemotherapy

Tracking Information
First Submitted Date ICMJE	August 19, 2010
First Posted Date ICMJE	August 23, 2010
Last Update Posted Date	April 29, 2015
Study Start Date ICMJE	December 2010
Actual Primary Completion Date	July 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: April 19, 2012)	The Progression Free Survival (PFS) of maintenance OSI-906 plus erlotinib, or placebo plus erlotinib in patients with nonprogression following four cycles of first-line platinum-based chemotherapy for advanced NSCLC in the overall population [ Time Frame: 22 months ]; PFS is defined as the time from randomization to disease progression based on RECIST v1.1 or death due to any cause whichever comes first
Original Primary Outcome Measures ICMJE; (submitted: August 19, 2010)	The Progression Free Survival (PFS) of maintenance OSI-906 plus erlotinib (Arm A), or erlotinib and placebo (Arm B) in patients with nonprogression following four cycles of first-line platinum-based chemotherapy for advanced NSCLC [ Time Frame: 22 months ]
Change History	Complete list of historical versions of study NCT01186861 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: January 2, 2013)	Overall survival (OS) [ Time Frame: 27 months ]The time from the date of randomization until the documented date of death; Disease control Rate (DCR) [ Time Frame: 27 months ]The proportion of patients with a best overall response of continued Complete Response (CR), CR, Partial Response (PR), OR Stable Disease (SD) based on RECIST criteria; Best overall response rate (ORR) [ Time Frame: 27 months ]The proportion of patients with a best overall response of CR or PR based on RECIST criteria; Response upgrade rate (RUR) [ Time Frame: 27 months ]The proportion of patients with a response upgrade; Duration of response [ Time Frame: 27 months ]The time from the date of the first documented response (CR/PR) to documented progression or death due to underlying cancer; Safety assessed through physical examination, vital signs, clinical laboratory tests, electrocardiograms (ECG) and Adverse Events [ Time Frame: 27 months ]
Original Secondary Outcome Measures ICMJE; (submitted: August 19, 2010)	PFS in epithelial phenotype E-cadherin 'positive' subpopulation and refine the E-cadherin 'positive' expression cut point for PFS benefit; [ Time Frame: 26.7 months ]; Disease control (DCR), response upgrade rate (RUR), best overall response rate (ORR), duration of response, and overall survival (OS); [ Time Frame: 26.7 months ]; Safety profile of OSI-906/erlotinib combination; [ Time Frame: 26.7 months ]; Pharmacokinetic (PK) profile of OSI-906/erlotinib combination; and [ Time Frame: 26.7 months ]; Exploratory biomarkers and correlations with treatment outcome [ Time Frame: 26.7 months ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Phase 2 Study of Maintenance OSI-906 Plus Erlotinib (Tarceva®), or Placebo Plus Erlotinib in Patients With Nonprogression Following 4 Cycles of Platinum-based Chemotherapy
Official Title ICMJE	A Randomized, Double-Blind, Placebo-controlled Phase 2 Study of Maintenance OSI-906 Plus Erlotinib (Tarceva®), or Erlotinib Plus Placebo in Patients With Nonprogression Following Four Cycles of 1st-line Platinum-based Chemotherapy for Advanced NSCLC
Brief Summary	A multicenter, randomized, double-blind, placebo-controlled, phase 2 study with a 1:1 randomization scheme.
Detailed Description	Adult patients with advanced Non-small Cell Lung Cancer (NSCLC) and nonprogression after platinum-based chemotherapy will be randomized 1:1 to receive either OSI-906 plus erlotinib or placebo plus erlotinib.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Non-Small Cell Lung Cancer (NSCLC) With Nonprogression Following 4 Cycles of Platinum-based Chemotherapy
Intervention ICMJE	Drug: OSI-906 Tablet administered with food and with up to 200 mL of water; Drug: erlotinib Tablet administered at least 2 hours after food with up to 200 mL of water Other Names: OSI-774 Tarceva; Drug: placebo Tablet administered at least 2 hours after food with up to 200 mL of water
Study Arms	Experimental: Arm A: OSI-906 plus erlotinib OSI-906 150 mg twice daily (BID) starting on Day 1; erlotinib 150 mg once daily (QD) starting on Day 1 Interventions: Drug: OSI-906 Drug: erlotinib; Placebo Comparator: Arm B: placebo plus erlotinib placebo BID starting on Day 1: erlotinib 150 mg QD starting on Day 1 Interventions: Drug: erlotinib Drug: placebo
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: June 6, 2013)	205
Original Estimated Enrollment ICMJE; (submitted: August 19, 2010)	200
Actual Study Completion Date	March 2015
Actual Primary Completion Date	July 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Histologically confirmed locally advanced or metastatic stage IIIB or IV NSCLC; Have experienced Complete Response (CR), Partial Response (PR) or Stable Disease (SD) following completion of 4 cycles of first-line platinum-based chemotherapy and are not progressing at time of entry into study (prior completed first-line combination bevacizumab therapy is permitted; however, current use of maintenance bevacizumab is not permitted. A maximum interval of 28 days between the last day of the treatment cycle and randomization; Patient has recovered from prior chemotherapy-related toxicity to ≤ grade 2; EGFR mutation status must be confirmed for participation in the study. EGFR analysis 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 APGD 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 centrally for biomarker 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 (for those patients with PR or SD after first-line platinum-based chemotherapy) according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1); Eastern Cooperative Oncology Group (ECOG) Performance Status(PS) 0 - 1; Previous adjuvant or neo-adjuvant treatment is permitted; Must be able to take oral medication; Fasting glucose ≤ 150 mg/dL (8.3 mmol/L). Concurrent use of non-insulinotropic antihyperglycemic therapy is permitted if the dose has been stable for ≥ 4 weeks at the time of randomization; Adequate hematopoietic, hepatic, and renal function defined as follows: Neutrophil count ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) AST and ALT ≤ 2.5 x ULN, or ≤ 5 x ULN if patient has documented liver metastases Serum creatinine ≤ 1.5 x ULN; Potassium, magnesium and calcium within normal limits (supplementation and retesting is permitted) Female patient must be either: Of non child bearing potential: post-menopausal (defined as at least 1 year without any menses) prior to Screening, or documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening); Or, if of childbearing potential: must have a negative urine pregnancy test at Screening, and must use two forms of birth control (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; Female patient must not be breastfeeding at Screening or during the study period and for 30 days after final study drug administration; Female patient must not donate ova starting at Screening and throughout the study period and for 30 days after final study drug administration; Male patient 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; Male patient must not donate sperm starting at Screening and throughout the study period and for at least 30 days after final study drug administration; Prior radiation therapy is permitted provided patients have recovered from 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 performed 21 days prior to randomization and adequate wound healing has occurred prior to randomization; Patients must provide written (signed) informed consent to participate in the study and for use of tumor tissues Exclusion Criteria: Prior exposure to agents directed at the Human Epidermal Receptor (HER) axis (eg, erlotinib, gefitinib, cetuximab, and trastuzumab); Malignancies other than NSCLC within 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); Type 1 diabetes mellitus or Type 2 diabetes mellitus currently requiring insulinotropic or insulin therapy; Prior insulin-like growth factor receptor (IGF-1R); Prior investigational agent within 21 days prior to randomization; Concurrent use of maintenance bevacizumab; History of poorly controlled gastrointestinal disorders that could affect the absorption of study drug (eg, Crohn's disease, ulcerative colitis, etc); History (within last 180 days) 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 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 based on independent central reviewer analysis of screening visit ECGs; Use of drugs that have a known risk of causing Torsades de Pointes (TdP) are prohibited within 14 days prior to randomization; Use of the potent CYP1A2 inhibitors ciprofloxacin and fluvoxamine. Other less potent CYP1A2 inhibitors/inducers are not excluded; Use of potent CYP3A4 inhibitor such as ketoconazole, clarithromycin, atazanavir, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), or voriconazole; Use of proton pump inhibitors such as omeprazole. Use of H2-receptor antagonists such as ranitidine are not excluded; History of cerebrovascular accident (CVA) within 180 days prior to randomization or that resulted in ongoing neurologic instability; Active infection, serious underlying medical condition (including any type of active seizure disorder within 12 months prior to randomization), or serious chronic illness that would impair the ability of the patient to receive study drug; 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; Symptomatic brain metastases that are not stable, require steroids, or that have required radiation and/or other related treatment (e.g., anti-epileptic medication) within 21 days prior to randomization; History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drug; 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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Brazil, Canada, Germany, Korea, Republic of, Poland, Romania, Russian Federation, United Kingdom, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01186861
Other Study ID Numbers ICMJE	OSI-906-205; 2010-020916-12 ( EudraCT Number )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Astellas Pharma Inc
Study Sponsor ICMJE	Astellas Pharma Inc
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Medical Director Astellas Pharma Global Development
PRS Account	Astellas Pharma Inc
Verification Date	April 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP