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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01186861
First received: August 19, 2010
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

A multicenter, randomized, double-blind, placebo-controlled, phase 2 study with a 1:1 randomization scheme.


Condition Intervention Phase
Non-Small Cell Lung Cancer (NSCLC) With Nonprogression Following 4 Cycles of Platinum-based Chemotherapy
Drug: OSI-906
Drug: erlotinib
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: 27 months ] [ Designated as safety issue: No ]
    The time from the date of randomization until the documented date of death

  • Disease control Rate (DCR) [ Time Frame: 27 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The proportion of patients with a response upgrade

  • Duration of response [ Time Frame: 27 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

Enrollment: 205
Study Start Date: December 2010
Estimated Study Completion Date: December 2014
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
Placebo Comparator: Arm B: placebo plus erlotinib
placebo BID starting on Day 1: erlotinib 150 mg QD starting on Day 1
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01186861

  Show 69 Study Locations
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Director: Medical Director Astellas Pharma Global Development
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01186861     History of Changes
Other Study ID Numbers: OSI-906-205, 2010-020916-12
Study First Received: August 19, 2010
Last Updated: June 19, 2014
Health Authority: United States: Food and Drug Administration
Brazil: Ministry of Health
Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices
Korea: Food and Drug Administration
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Astellas Pharma Inc:
NSCLC
Erlotinib
OSI-906
Placebo
Platinum-based chemotherapy

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014