A Phase 1b/2 Study of OMP-59R5 (Tarextumab) in Combination With Etoposide and Platinum Therapy

NCT01859741 | Terminated Phase 1 Results DMC

• 1 other identifier: 59R5-003
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 35

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.

Conditions

Stage IV Small Cell Lung Cancer

Keywords

Newly diagnosed Stage IV Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (4)

• 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)

  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.

  Up to 1 year in absence of unacceptable toxicity or disease progression.

• Phase 1b: Overall Response (Response Evaluable Population)

  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.

  Up to 1 year in absence of unacceptable toxicity or disease progression.

• Phase 2: Progression Free Survival (ITT Population)

  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.

  Up to 1 year until disease progression or death.

• Phase 2: Best Overall Tumor Response Based on Investigator Assessment (ITT Population)

  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.

  Up to 1 year in absence of unacceptable toxicity or disease progression

Study Arms (2)

OMP-59R5 Combination with Etoposide and Cisplatin

EXPERIMENTAL

Drug: OMP-59R5; Drug: Etoposide; Drug: Placebo; Drug: Cisplatin or Carboplatin

Etoposide and Cisplatin plus Placebo

EXPERIMENTAL

Drug: OMP-59R5; Drug: Etoposide; Drug: Placebo; Drug: Cisplatin or Carboplatin

Interventions

OMP-59R5 DRUG

OMP-59R5 administered intravenously

Also known as: Tarextumab

Etoposide and Cisplatin plus Placebo; OMP-59R5 Combination with Etoposide and Cisplatin

Etoposide DRUG

administered intravenously

Etoposide and Cisplatin plus Placebo; OMP-59R5 Combination with Etoposide and Cisplatin

Placebo DRUG

administered IV

Etoposide and Cisplatin plus Placebo; OMP-59R5 Combination with Etoposide and Cisplatin

Cisplatin or Carboplatin DRUG

administered intravenously

Etoposide and Cisplatin plus Placebo; OMP-59R5 Combination with Etoposide and Cisplatin

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• Prior therapy including radiation, chemotherapy or surgery for newly diagnosed extensive stage small cell lung cancer.
• 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.
• Females who are pregnant or breastfeeding.
• Concurrent use of therapeutic warfarin (prophylactic low dose of warfarin, i.e., 1 mg daily for port catheter is allowed)

Sponsors & Collaborators

• OncoMed Pharmaceuticals, Inc.: lead

Study Sites (35)

Highlands Oncology Group

Rogers, Arkansas, 72758, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Sarah Cannon

Fort Myers, Florida, 33905, United States

Location

Ocala Oncology Center, PL

Ocala, Florida, 34474, United States

Location

Piedmont Cancer Institute

Atlanta, Georgia, 30318, United States

Location

Georgia Cancer Specialists, PC

Atlanta, Georgia, 30341, United States

Location

Univeristy of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

University of Maryland, Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Weinberg Cancer Institute

Baltimore, Maryland, 21237, United States

Location

University of Michigan Medical Center, Clinical Trials Office

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Minnesota Oncology Hematology , P.A.

Minneapolis, Minnesota, 55404, United States

Location

Oncology Hematology West PC, dba Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Oncology Hematology Care, Inc.

Cincinnati, Ohio, 45242, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Providence Cancer Center Oncology and Hematology Care Eastside

Portland, Oregon, 97213, United States

Location

UPMC Cancer Pavilion

Pittsburgh, Pennsylvania, 15232, United States

Location

Greenville Health System, Clinical Research Unit, Institute for Translational Oncology Research

Greenville, South Carolina, 29605, United States

Location

Tennessee Oncology, PLLC

Chattanooga, Tennessee, 37404, United States

Location

The Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Texas Oncology-South Austin

Austin, Texas, 78745, United States

Location

Texas Oncology-Bedford

Bedford, Texas, 76022, United States

Location

Texas Oncology, P.A.

Dallas, Texas, 75246, United States

Location

The University of Texas MD A nderson Cancer Center

Houston, Texas, 77030, United States

Location

Cancer Care Network of South Texas

San Antonio, Texas, 78217, United States

Location

Oncology and Hematology Associates of Southwest Virginia Inc.

Blacksburg, Virginia, 24060, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

tarextumab; Etoposide; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes

Results Point of Contact

• Title: Manager, Regulatory Affairs
• Organization: OncoMed Pharmaceuticals, Inc.

imran.chaudhry@oncomed.com

6509958322

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2013
• First Posted: May 22, 2013
• Study Start: January 7, 2012
• Primary Completion: April 18, 2017
• Study Completion: May 8, 2017
• Last Updated: September 9, 2020
• Results First Posted: May 1, 2019

Record last verified: 2020-09

Locations

US (35)