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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01186861
Recruitment Status : Completed
First Posted : August 23, 2010
Last Update Posted : September 5, 2018
Information provided by (Responsible Party):
Astellas Pharma Inc

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

Condition or disease Intervention/treatment 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

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 : Interventional  (Clinical Trial)
Actual Enrollment : 205 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Actual Study Start Date : March 4, 2011
Actual Primary Completion Date : July 1, 2013
Actual Study Completion Date : March 11, 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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

Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: 27 months ]
    The time from the date of randomization until the documented date of death

  2. 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

  3. 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

  4. Response upgrade rate (RUR) [ Time Frame: 27 months ]
    The proportion of patients with a response upgrade

  5. 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

  6. Safety assessed through physical examination, vital signs, clinical laboratory tests, electrocardiograms (ECG) and Adverse Events [ Time Frame: 27 months ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01186861

  Hide Study Locations
United States, Florida
Site US10007
Jacksonville, Florida, United States, 32207
Site US10001
Port Saint Lucie, Florida, United States, 34952
United States, Georgia
Site US10002
Albany, Georgia, United States, 31701
United States, Illinois
Site US10008
Chicago, Illinois, United States, 60612
United States, Maine
Site US10011
Scarborough, Maine, United States, 04074
United States, North Carolina
Site US10004
Greensboro, North Carolina, United States, 27403
Site US10010
Winston-Salem, North Carolina, United States, 27103
Site BR55005
Barretos, Brazil, 14784-400
Site BR55004
Brasilia, Brazil, 70840-050
Site BR55015
Cachoeiro de Itapemirim, Brazil, 29308-014
Site BR55011
Florianopolis, Brazil, 88034-000
Site BR55003
Fortaleza, Brazil, 60336-550
Site BR55016
Goiania, Brazil, 74605-030
Site BR55006
Ijui, Brazil, 98700-000
Site BR55001
Itajai, Brazil, 88301-220
Site BR55008
Piracicaba, Brazil, 13419-155
Site BR55013
Porto Alegre, Brazil, 90430-090
Site BR55014
Porto Alegre, Brazil, 90610-000
Site BR55012
Ribeirao Preto, Brazil, 14515-130
Site BR55002
Rio de Janeiro, Brazil, 20231-050
Site BR55007
Sao Paulo, Brazil, 01323-920
Site CA11001
Oshawa, Canada, L1G 2B9
Site CA11004
Ottawa, Canada, K1H 8L6
Site CA11006
Toronto, Canada, M5G 1X5
Site CA11002
Toronto, Canada, M6R 1B5
Site DE49014
Berlin, Germany, 10117
Site DE49011
Dortmund, Germany, 44145
Site DE49003
Grosshansdorf, Germany, 22977
Site DE49001
Heidelberg, Germany, 69126
Site DE49002
Hemer, Germany, 58675
Site DE49009
Homburg/Saar, Germany, 66421
Site DE49006
Immenhausen, Germany, 34376
Site DE49012
Karlsruhe, Germany, 76137
Site DE49015
Kassel, Germany, 34125
Site DE49008
Koln, Germany, 51109
Site DE49010
Lubeck, Germany, 23538
Site DE49013
Mainz, Germany, 55131
Site DE49005
Minden, Germany, 32429
Korea, Republic of
Site KR82007
Busan, Korea, Republic of, 602-715
Site KR82006
Hwasun, Korea, Republic of, 519-809
Site KR82008
Incheon, Korea, Republic of, 400-711
Site KR82004
Seongnam-si, Korea, Republic of, 463-707
Site KR82003
Seoul, Korea, Republic of, 120-752
Site KR82005
Seoul, Korea, Republic of, 135-710
Site KR82002
Seoul, Korea, Republic of, 137-701
Site KR82001
Suwon, Korea, Republic of
Site PL48002
Elblag, Poland, 82-300
Site PL48005
Szczecin, Poland, 70-891
Site PL48008
Torun, Poland, 87-100
Site PL48006
Wroclaw, Poland, 53-439
Site RO40005
Alba Iulia, Romania, 510077
Site RO40001
Baia Mare, Romania, 490110
Site RO40007
Brasov, Romania, 500366
Site RO40002
Cluj-Napoca, Romania, 400015
Site RO40003
Cluj-Napoca, Romania, 400015
Site RO40006
Craiova, Romania, 200535
Site RO40004
Hunedoara, Romania, 331057
Russian Federation
Site RU70002
Chelaybinsk, Russian Federation, 454087
Site RU70010
Kazan, Russian Federation, 420029
Site RU70007
Saint Petersburg, Russian Federation, 194291
Site RU70009
Saint Petersburg, Russian Federation, 197089
Site RU70011
Saint Petersburg, Russian Federation, 197089
United Kingdom
Site GB44007
Bristol, United Kingdom, BS2 8ED
Site GB44006
Dundee, United Kingdom, DD1 9SY
Site GB44003
Leeds, United Kingdom, LS9 7TF
Site GB44002
Leicester, United Kingdom, LE1 5WW
Site GB44005
London, United Kingdom, NW1 2PQ
Site GB44001
Manchester, United Kingdom, M20 4BX
Site GB44004
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
Astellas Pharma Inc
Study Director: Medical Director Astellas Pharma Global Development

Additional Information:
Responsible Party: Astellas Pharma Inc Identifier: NCT01186861     History of Changes
Other Study ID Numbers: OSI-906-205
2010-020916-12 ( EudraCT Number )
First Posted: August 23, 2010    Key Record Dates
Last Update Posted: September 5, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Access to anonymized individual participant level data collected during the trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
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.
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.

Keywords provided by Astellas Pharma Inc:
Platinum-based chemotherapy

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