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
- Conditions
- Non-Small Cell Lung Cancer (NSCLC) With Nonprogression Following 4 Cycles of Platinum-based Chemotherapy
- Interventions
- Registration Number
- NCT01186861
- Lead Sponsor
- Astellas Pharma Inc
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 205
-
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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: placebo plus erlotinib erlotinib placebo BID starting on Day 1: erlotinib 150 mg QD starting on Day 1 Arm A: OSI-906 plus erlotinib OSI-906 OSI-906 150 mg twice daily (BID) starting on Day 1; erlotinib 150 mg once daily (QD) starting on Day 1 Arm B: placebo plus erlotinib placebo placebo BID starting on Day 1: erlotinib 150 mg QD starting on Day 1 Arm A: OSI-906 plus erlotinib erlotinib OSI-906 150 mg twice daily (BID) starting on Day 1; erlotinib 150 mg once daily (QD) starting on Day 1
- Primary Outcome Measures
Name Time Method 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 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
Name Time Method Disease control Rate (DCR) 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) 27 months The proportion of patients with a best overall response of CR or PR based on RECIST criteria
Response upgrade rate (RUR) 27 months The proportion of patients with a response upgrade
Safety assessed through physical examination, vital signs, clinical laboratory tests, electrocardiograms (ECG) and Adverse Events 27 months Overall survival (OS) 27 months The time from the date of randomization until the documented date of death
Duration of response 27 months The time from the date of the first documented response (CR/PR) to documented progression or death due to underlying cancer
Trial Locations
- Locations (69)
Site US10004
🇺🇸Greensboro, North Carolina, United States
Site PL48005
🇵🇱Szczecin, Poland
Site RO40005
🇷🇴Alba Iulia, Romania
Site KR82003
🇰🇷Seoul, Korea, Republic of
Site RO40003
🇷🇴Cluj-Napoca, Romania
Site PL48006
🇵🇱Wroclaw, Poland
Site US10007
🇺🇸Jacksonville, Florida, United States
Site KR82004
🇰🇷Seongnam-si, Korea, Republic of
Site BR55013
🇧🇷Porto Alegre, Brazil
Site US10011
🇺🇸Scarborough, Maine, United States
Site BR55004
🇧🇷Brasilia, Brazil
Site BR55008
🇧🇷Piracicaba, Brazil
Site US10001
🇺🇸Port Saint Lucie, Florida, United States
Site US10002
🇺🇸Albany, Georgia, United States
Site US10010
🇺🇸Winston-Salem, North Carolina, United States
Site CA11002
🇨🇦Toronto, Canada
Site BR55015
🇧🇷Cachoeiro de Itapemirim, Brazil
Site DE49001
🇩🇪Heidelberg, Germany
Site US10008
🇺🇸Chicago, Illinois, United States
Site BR55014
🇧🇷Porto Alegre, Brazil
Site DE49003
🇩🇪Grosshansdorf, Germany
Site BR55003
🇧🇷Fortaleza, Brazil
Site DE49014
🇩🇪Berlin, Germany
Site CA11001
🇨🇦Oshawa, Canada
Site CA11004
🇨🇦Ottawa, Canada
Site DE49011
🇩🇪Dortmund, Germany
Site BR55011
🇧🇷Florianopolis, Brazil
Site BR55012
🇧🇷Ribeirao Preto, Brazil
Site BR55001
🇧🇷Itajai, Brazil
Site DE49002
🇩🇪Hemer, Germany
Site DE49009
🇩🇪Homburg/Saar, Germany
Site DE49015
🇩🇪Kassel, Germany
Site DE49010
🇩🇪Lubeck, Germany
Site DE49005
🇩🇪Minden, Germany
Site BR55016
🇧🇷Goiania, Brazil
Site BR55005
🇧🇷Barretos, Brazil
Site BR55006
🇧🇷Ijui, Brazil
Site BR55002
🇧🇷Rio de Janeiro, Brazil
Site BR55007
🇧🇷Sao Paulo, Brazil
Site CA11006
🇨🇦Toronto, Canada
Site DE49006
🇩🇪Immenhausen, Germany
Site DE49012
🇩🇪Karlsruhe, Germany
Site KR82001
🇰🇷Suwon, Korea, Republic of
Site DE49013
🇩🇪Mainz, Germany
Site DE49008
🇩🇪Koln, Germany
Site KR82007
🇰🇷Busan, Korea, Republic of
Site KR82006
🇰🇷Hwasun, Korea, Republic of
Site KR82008
🇰🇷Incheon, Korea, Republic of
Site KR82002
🇰🇷Seoul, Korea, Republic of
Site KR82005
🇰🇷Seoul, Korea, Republic of
Site RO40001
🇷🇴Baia Mare, Romania
Site PL48002
🇵🇱Elblag, Poland
Site RO40007
🇷🇴Brasov, Romania
Site PL48008
🇵🇱Torun, Poland
Site RO40006
🇷🇴Craiova, Romania
Site RU70010
🇷🇺Kazan, Russian Federation
Site RO40002
🇷🇴Cluj-Napoca, Romania
Site RO40004
🇷🇴Hunedoara, Romania
Site RU70002
🇷🇺Chelaybinsk, Russian Federation
Site RU70007
🇷🇺Saint Petersburg, Russian Federation
Site RU70009
🇷🇺Saint Petersburg, Russian Federation
Site RU70011
🇷🇺Saint Petersburg, Russian Federation
Site GB44003
🇬🇧Leeds, United Kingdom
Site GB44007
🇬🇧Bristol, United Kingdom
Site GB44001
🇬🇧Manchester, United Kingdom
Site GB44002
🇬🇧Leicester, United Kingdom
Site GB44004
🇬🇧Southampton, United Kingdom
Site GB44006
🇬🇧Dundee, United Kingdom
Site GB44005
🇬🇧London, United Kingdom