Clinical trial NCT01859741: A Phase 1b/2 Study of OMP-59R5 (Tarextumab) in Combination With Etoposide and Platinum Therapy
Official title: A Phase 1b/2 Study of OMP-59R5 in Combination With Etoposide and Platinum Therapy in Subjects With Untreated Extensive Stage Small Cell Lung Cancer (PINNACLE)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Stage IV Small Cell Lung Cancer
Keywords: Newly diagnosed Stage IV Small Cell Lung Cancer
Lead sponsor: Mereo BioPharma
Sponsor class: INDUSTRY
First posted: 2013-05-22
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

Subjects must meet all of the following criteria to be eligible for the study:

1. Histologically or cytologically documented extensive stage small cell lung cancer.
2. Adults of 18 years of age or older.
3. Performance Status (ECOG) of 0 or 1.
4. Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.
5. Adequate organ function:

   1. Adequate hematologic function (absolute neutrophil count \[ANC\] ≥ 1,500 cells/μL; hemoglobin ≥ 9 g/dL, platelets ≥ 100,000/μL).
   2. Adequate renal function (serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 60 mL/min using Cockcroft-Gault formula).
   3. 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).
   4. Prothrombin Time (PT)/International Normalized Ration (INR) ≤1.5 × ULN, activated partial thromboplastin time (aPTT) ≤1.5 × ULN.
6. Written consent on an Institutional Review Board (IRB)/IndependentEthics Committee (IEC)-approved Informed Consent Form prior to any study-specific evaluation.
7. 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.
8. 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.

Exclusion Criteria:

Subjects who meet any of the following criteria will not be eligible for participation in the study:

1. Limited stage small cell lung cancer appropriate for radical treatment with chemoradiation.
2. Prior therapy including radiation, chemotherapy or surgery for newly diagnosed extensive stage small cell lung cancer.
3. 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.
4. 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.
5. A history of malignancy with the exception of:

   1. Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer
   2. Adequately treated stage I cancer from which the subject is currently in remission, or
   3. Any other cancer from which the subject has been disease-free for ≥ 3 years
6. Known human immunodeficiency virus (HIV) infection.
7. Females who are pregnant or breastfeeding.
8. Concurrent use of therapeutic warfarin (prophylactic low dose of warfarin, i.e., 1 mg daily for port catheter is allowed)

Primary outcomes:
measure: 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)
timeFrame: Up to 1 year in absence of unacceptable toxicity or disease progression.
measure: Phase 1b: Overall Response (Response Evaluable Population)
timeFrame: Up to 1 year in absence of unacceptable toxicity or disease progression.
measure: Phase 2: Progression Free Survival (ITT Population)
timeFrame: Up to 1 year until disease progression or death.
measure: Phase 2: Best Overall Tumor Response Based on Investigator Assessment (ITT Population)
timeFrame: Up to 1 year in absence of unacceptable toxicity or disease progression
Secondary outcomes:
Other outcomes:
Locations:
city: Rogers
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Fort Myers
country: United States
facility: Sarah Cannon
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center, PL
state: Florida
city: Atlanta
country: United States
facility: Piedmont Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Georgia Cancer Specialists, PC
state: Georgia
city: Chicago
country: United States
facility: Univeristy of Chicago Medical Center
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland, Greenebaum Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Weinberg Cancer Institute
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center, Clinical Trials Office
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology , P.A.
state: Minnesota
city: Omaha
country: United States
facility: Oncology Hematology West PC, dba Nebraska Cancer Specialists
state: Nebraska
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Portland
country: United States
facility: Providence Cancer Center Oncology and Hematology Care Eastside
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC Cancer Pavilion
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Health System, Clinical Research Unit, Institute for Translational Oncology Research
state: South Carolina
city: Chattanooga
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology-South Austin
state: Texas
city: Bedford
country: United States
facility: Texas Oncology-Bedford
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Houston
country: United States
facility: The University of Texas MD A nderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Network of South Texas
state: Texas
city: Blacksburg
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia Inc.
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
Study officials:
References: