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.
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

May 16, 2013
March 19, 2014
May 2013
October 2015   (final data collection date for primary outcome measure)
  • 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
  • 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 pts treated with OMP-59R5 in combination with etoposide and cisplain
  • 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
Complete list of historical versions of study NCT01859741 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 termined 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 responseat each tumor assessment
  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Every 3 weeks till the pt comes off the study treatment, up to 25 months ] [ Designated as safety issue: No ]
    AEs, laboratory assessment and physical examination.
Not Provided
Not Provided
 
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)
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)

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.

Not Provided
Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Stage IV Small Cell Lung Cancer
  • 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: OMP-59R5 Combination with Etoposide and Cisplatin
    Interventions:
    • Drug: OMP-59R5
    • Drug: Etoposide
    • Drug: Placebo
    • Drug: Cisplatin
  • Experimental: Etoposide and Cisplatin plus Placebo
    Interventions:
    • Drug: OMP-59R5
    • Drug: Etoposide
    • Drug: Placebo
    • Drug: Cisplatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
80
July 2017
October 2015   (final data collection date for primary outcome measure)

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)
Both
18 Years to 90 Years
No
Contact: Jakob Dupont, MA, MD 650-995-8307 jakob.dupont@oncomed.com
United States
 
NCT01859741
59R5-003
Yes
OncoMed Pharmaceuticals, Inc.
OncoMed Pharmaceuticals, Inc.
Not Provided
Principal Investigator: Lowell L. Hart, M.D., F.A.C.P. Florida Cancer Specialists & Research Institute
OncoMed Pharmaceuticals, Inc.
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP