A Phase 1b/2 Study of OMP-59R5 in Combination With Etoposide and Cisplatin in Subjects With Untreated Extensive Stage Small Cell Lung Cancer (PINNACLE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by OncoMed Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
OncoMed Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01859741
First received: May 16, 2013
Last updated: March 19, 2014
Last verified: March 2014
  Purpose

The study consists of a Phase1b lead-in portion to determine the MTD of OMP-59R5 in combination with EP for 6 cycles followed a Phase 2, multicenter, 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.


Condition Intervention Phase
Stage IV Small Cell Lung Cancer
Drug: OMP-59R5
Drug: Etoposide
Drug: Placebo
Drug: Cisplatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Study of OMP-59R5 in Combination With Etoposide and Cisplatin in Subjects With Untreated Extensive Stage Small Cell Lung Cancer (PINNACLE)

Resource links provided by NLM:


Further study details as provided by OncoMed Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Dose limiting toxicities (DLT) of OMP-59R5 in combination with Etoposide and Cisplatin [ Time Frame: Subjects will be treated and observed for DLT through the end of the first cycle (28 days) ] [ Designated as safety issue: Yes ]
    The maximum tolerated dose (MTD) will be determined in patients treated with OMP-59R5 in combination with etoposide and cisplatin

  • Progression-free survival [ Time Frame: Number of days from randomization until death or disease progression, assessed up 25 months ] [ Designated as safety issue: No ]
    To determine the clinical benefit, as measured by progression free survival of the addition OMP-59R5 to etoposide and cisplatin in subjects who are receiving first-line therapy for extensive stage small cell lung cancer


Secondary Outcome Measures:
  • PK of OMP-59R5 when given in combination with Etoposide and Cisplatin. [ Time Frame: Days 1, 3 and 8 of Cycle 1 and 3, and treatment termination ] [ Designated as safety issue: No ]
    PK of OMP-59R5 when given in combination with etoposide and cisplatin. Plasma samples from all subjects enrolled in Phase 1 b portion of the study will be obtained for PK analysis at pre-infusion, approximately 5 minutes post infusion on Day 1 of cycles 1 and 3, and Day 8 of cycles 1 and 3 as well as when the subject is terminated from study treatment of OMP-59R5. Pharmacokinetic parameters (i.e. area under the curve [AUC], clearance, volume of distribution and apparent half life) of OMP-59R5 will be assessed for each evaluable subject.

  • Overall survival, 12 month OS and overall response rate [ Time Frame: Throughout the study, and approximately every 6 weeks after the treatment termination ] [ Designated as safety issue: No ]
    Survival status, anti-cancer treatment during the survival follow-up after the treatment termination, overall response at each tumor assessment

  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Every 3 weeks till the patient comes off the study treatment, up to 25 months ] [ Designated as safety issue: No ]
    AEs, laboratory assessment and physical examination.


Estimated Enrollment: 80
Study Start Date: May 2013
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OMP-59R5 Combination with Etoposide and Cisplatin Drug: OMP-59R5
OMP-59R5 administered intravenously
Other Name: OMP-59R5
Drug: Etoposide
administered intravenously
Other Name: Etoposide
Drug: Placebo
administered IV
Other Name: Placebo
Drug: Cisplatin
administered intravenously
Other Name: Cisplatin
Experimental: Etoposide and Cisplatin plus Placebo Drug: OMP-59R5
OMP-59R5 administered intravenously
Other Name: OMP-59R5
Drug: Etoposide
administered intravenously
Other Name: Etoposide
Drug: Placebo
administered IV
Other Name: Placebo
Drug: Cisplatin
administered intravenously
Other Name: Cisplatin

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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. 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 >1.5xULN 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 IRB/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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01859741

Contacts
Contact: Jakob Dupont, MA, MD 650-995-8307 jakob.dupont@oncomed.com

Locations
United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Jonilyn Brown    310-652-3110    jonilyn.brown@cshs.org   
Contact: Cindi Martin    (310) 423-2276    cynthia.martin@cshs.org   
Principal Investigator: Alain Mita, MD         
United States, Colorado
Rocky Mountain Cancer Centers Recruiting
Denver, Colorado, United States, 80218
Contact: Robert M. Jotte, MD, PhD    303-388-4876      
Principal Investigator: Robert Jotte, MD, PhD         
United States, Florida
Florida Cancer Specialists & Research Institute Recruiting
Fort Myers, Florida, United States, 33905
Contact: Lowell L. Hart, M.D., F.A.C.P.    239-938-0800    llhart@flcancer.com   
Principal Investigator: Lowell L. Hart, M.D., F.A.C.P.         
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Payal Patel    646-888-4359    patelp6@mskcc.org   
Principal Investigator: Maria C. Pietanza, MD         
United States, South Carolina
Greenville Health System, Clinical Research Unit, Institute for Translational Oncology Research Recruiting
Greenville, South Carolina, United States, 29605
Contact: William L Gluck, MD    864-232-2820    lgluck@ghs.org   
Principal Investigator: William L Gluck, MD         
United States, Tennessee
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
Contact: David Spigel, MD    615-329-7274      
Principal Investigator: David Spigel, MD         
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Contact: Melanie Herrin    703-208-3188    melanie.herrin@usoncology.com   
Principal Investigator: Alexander I. Spira, MD         
Sponsors and Collaborators
OncoMed Pharmaceuticals, Inc.
Investigators
Principal Investigator: Lowell L. Hart, M.D., F.A.C.P. Florida Cancer Specialists & Research Institute
  More Information

No publications provided

Responsible Party: OncoMed Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01859741     History of Changes
Other Study ID Numbers: 59R5-003
Study First Received: May 16, 2013
Last Updated: March 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by OncoMed Pharmaceuticals, Inc.:
Newly diagnosed Stage IV Small Cell Lung Cancer

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Etoposide phosphate
Cisplatin
Etoposide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014