A Phase 1b/2 Study of OMP-59R5 (Tarextumab) in Combination With Etoposide and Platinum Therapy
- Conditions
- Stage IV Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT01859741
- Lead Sponsor
- OncoMed Pharmaceuticals, Inc.
- Brief Summary
The study consists of a Phase1b lead-in portion to determine the maximum tolerated dose (MTD) of OMP-59R5 (tarextumab) in combination with etoposide (EP) for 6 cycles followed a Phase 2, multi center, randomized, placebo-controlled portion comparing the efficacy and safety of OMP-59R5 in combination with EP for 6 cycles followed by single agent OMP-59R5 relative to EP alone for 6 cycles in subjects receiving first-line therapy for extensive stage small cell lung cancer.
- Detailed Description
The Phase 1b lead-in portion of the study was conducted to determine the MTD of OMP-59R5 administered along with EP. The Phase 2 portion of the study was multi-center, randomized, and placebo-controlled. Subjects who qualified for enrollment into the Phase 2 portion of the study were randomized in a 1:1 ratio to receive study treatment of tarextumab along with EP (Arm A) or placebo along with EP (Arm B).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 172
Subjects must meet all of the following criteria to be eligible for the study:
-
Histologically or cytologically documented extensive stage small cell lung cancer.
-
Adults of 18 years of age or older.
-
Performance Status (ECOG) of 0 or 1.
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Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.
-
Adequate organ function:
- Adequate hematologic function (absolute neutrophil count [ANC] ≥ 1,500 cells/μL; hemoglobin ≥ 9 g/dL, platelets ≥ 100,000/μL).
- Adequate renal function (serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 60 mL/min using Cockcroft-Gault formula).
- Adequate hepatic function (alanine aminotransferase [ALT] ≤ 3 x upper limit of normal [ULN], ALT may be ≤ 5 x ULN if due to liver metastases but cannot be associated with concurrent elevated bilirubin >1.5 times the upper limit of normal (ULN) unless it is approved by the Sponsor's Medical Monitor).
- Prothrombin Time (PT)/International Normalized Ration (INR) ≤1.5 × ULN, activated partial thromboplastin time (aPTT) ≤1.5 × ULN.
-
Written consent on an Institutional Review Board (IRB)/IndependentEthics Committee (IEC)-approved Informed Consent Form prior to any study-specific evaluation.
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For women of child-bearing potential, negative serum pregnancy test at screening and use of physician-approved method of birth control from 30 days prior to the first study drug administration to 30 days following the last study drug administration or the last EP in the study, whichever is discontinued last.
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Male subjects must be surgically sterile or must agree to use physician-approved contraception during the study and for 30 days following the last study drug administration or the last EP in the study, whichever is discontinued last.
Subjects who meet any of the following criteria will not be eligible for participation in the study:
-
Limited stage small cell lung cancer appropriate for radical treatment with chemoradiation.
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Prior therapy including radiation, chemotherapy or surgery for newly diagnosed extensive stage small cell lung cancer.
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Presence of any serious or uncontrolled illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure unstable angina pectoris, uncontrolled cardiac arrhythmia, uncontrolled arterial thrombosis, symptomatic pulmonary embolism, and psychiatric illness that would limit compliance with study requirement.
-
History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty and/or stenting within 6 months prior to the first administration of study drug.
-
A history of malignancy with the exception of:
- Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer
- Adequately treated stage I cancer from which the subject is currently in remission, or
- Any other cancer from which the subject has been disease-free for ≥ 3 years
-
Known human immunodeficiency virus (HIV) infection.
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Females who are pregnant or breastfeeding.
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Concurrent use of therapeutic warfarin (prophylactic low dose of warfarin, i.e., 1 mg daily for port catheter is allowed)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Etoposide and Cisplatin plus Placebo Cisplatin or Carboplatin - Etoposide and Cisplatin plus Placebo OMP-59R5 - Etoposide and Cisplatin plus Placebo Placebo - OMP-59R5 Combination with Etoposide and Cisplatin OMP-59R5 - OMP-59R5 Combination with Etoposide and Cisplatin Placebo - OMP-59R5 Combination with Etoposide and Cisplatin Cisplatin or Carboplatin - Etoposide and Cisplatin plus Placebo Etoposide - OMP-59R5 Combination with Etoposide and Cisplatin Etoposide -
- Primary Outcome Measures
Name Time Method Phase 1b: Overall Response (Response Evaluable Population) Up to 1 year in absence of unacceptable toxicity or disease progression. The best overall response is defined as the best Investigator-assessed response recorded from the start of the treatment until disease progression in the following order of importance: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Not Evaluable (NE). Response evaluable population includes subjects who received 1 partial dose of OMP-59R5 and at at least 1 post tumor assessment.
Phase 1b: To Determine the Maximum Tolerated Dose (MTD) of OMP-59R5 When Administered With Etoposide and Cisplatin or Carboplatin (Number of Subjects With DLTs) Up to 1 year in absence of unacceptable toxicity or disease progression. To determine the MTD of tarextumab when administered on Day 1 of each 21 day cycle along with etoposide 100 mg/m2 on Days 1, 2 and 3, and cisplatin 80 mg/m2 or carboplatin area under the curve (AUC) of 5 mg/mL•min on Day 1 in subjects with untreated extensive stage small cell lung cancer. DLT evaluable population includes all subjects who received at least 1 partial dose of OMP-59R5 during the Phase 1b dose escalation portion of the study including the carboplatin cohort and who had completed Day 21 cycle of 1 OMP-59R5 administration or had discontinued due to drug-related toxicity.
Phase 2: Progression Free Survival (ITT Population) Up to 1 year until disease progression or death. To determine the improvement in Progression Free Survival (PFS) resulting from the addition of tarextumab to etoposide and platinum therapy (EP) in subjects receiving first-line therapy for extensive stage small cell lung cancer. PFS is based on the Investigator-assessments of tumor response which is defined as the number of days from randomization until death or disease progression as defined by RECIST criteria for the ITT Population.
Phase 2: Best Overall Tumor Response Based on Investigator Assessment (ITT Population) Up to 1 year in absence of unacceptable toxicity or disease progression The response rate is the number of subjects per treatment arm who have either a complete response (CR) or partial response (PR) for best overall response (according to RECIST criteria) divided by the number of subjects randomized to the respective arms.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (35)
Univeristy of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
University of Maryland, Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Highlands Oncology Group
🇺🇸Rogers, Arkansas, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Sarah Cannon
🇺🇸Fort Myers, Florida, United States
Ocala Oncology Center, PL
🇺🇸Ocala, Florida, United States
Piedmont Cancer Institute
🇺🇸Atlanta, Georgia, United States
Georgia Cancer Specialists, PC
🇺🇸Atlanta, Georgia, United States
Weinberg Cancer Institute
🇺🇸Baltimore, Maryland, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
UPMC Cancer Pavilion
🇺🇸Pittsburgh, Pennsylvania, United States
Greenville Health System, Clinical Research Unit, Institute for Translational Oncology Research
🇺🇸Greenville, South Carolina, United States
Texas Oncology-South Austin
🇺🇸Austin, Texas, United States
The University of Texas MD A nderson Cancer Center
🇺🇸Houston, Texas, United States
Texas Oncology, P.A.
🇺🇸Dallas, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Minnesota Oncology Hematology , P.A.
🇺🇸Minneapolis, Minnesota, United States
Oncology Hematology Care, Inc.
🇺🇸Cincinnati, Ohio, United States
Cancer Care Network of South Texas
🇺🇸San Antonio, Texas, United States
Texas Oncology-Bedford
🇺🇸Bedford, Texas, United States
Oncology and Hematology Associates of Southwest Virginia Inc.
🇺🇸Blacksburg, Virginia, United States
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
Yale University
🇺🇸New Haven, Connecticut, United States
University of Michigan Medical Center, Clinical Trials Office
🇺🇸Ann Arbor, Michigan, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Oncology Hematology West PC, dba Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Providence Cancer Center Oncology and Hematology Care Eastside
🇺🇸Portland, Oregon, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Tennessee Oncology, PLLC
🇺🇸Chattanooga, Tennessee, United States
The Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States