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

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

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

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer (NSCLC) With Nonprogression Following 4 Cycles of Platinum-based Chemotherapy
• Intervention / Treatment: Drug: OSI-906; Drug: erlotinib; Drug: placebo

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
• Enrollment (Actual): 205
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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: Tarceva; OSI-774
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: Tarceva; OSI-774; Drug: placebo; Tablet administered at least 2 hours after food with up to 200 mL of water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	22 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	The time from the date of randomization until the documented date of death	27 months
Disease control Rate (DCR)	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	27 months
Best overall response rate (ORR)	The proportion of patients with a best overall response of CR or PR based on RECIST criteria	27 months
Response upgrade rate (RUR)	The proportion of patients with a response upgrade	27 months
Duration of response	The time from the date of the first documented response (CR/PR) to documented progression or death due to underlying cancer	27 months
Safety assessed through physical examination, vital signs, clinical laboratory tests, electrocardiograms (ECG) and Adverse Events		27 months

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

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): March 4, 2011
• Primary Completion (ACTUAL): July 1, 2013
• Study Completion (ACTUAL): March 11, 2015

Study Registration Dates

• First Submitted: August 19, 2010
• First Submitted That Met QC Criteria: August 19, 2010
• First Posted (ESTIMATE): August 23, 2010

Study Record Updates

• Last Update Posted (ACTUAL): September 5, 2018
• Last Update Submitted That Met QC Criteria: August 31, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: NSCLC; Erlotinib; Platinum-based chemotherapy; Placebo; OSI-906
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: OSI-906-205; 2010-020916-12 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 www.clinicalstudydatarequest.com.
• 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