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

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ClinicalTrials.gov Identifier: NCT01859741
Recruitment Status : Terminated (OMP-59R5 did not improve PFS.)
First Posted : May 22, 2013
Results First Posted : May 1, 2019
Last Update Posted : September 9, 2020
Sponsor:
Information provided by (Responsible Party):
Mereo BioPharma ( OncoMed Pharmaceuticals, Inc. )

Study Description
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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.

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

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).
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 172 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : January 7, 2012
Actual Primary Completion Date : April 18, 2017
Actual Study Completion Date : May 8, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: OMP-59R5 Combination with Etoposide and Cisplatin Drug: OMP-59R5
OMP-59R5 administered intravenously
Other Name: Tarextumab

Drug: Etoposide
administered intravenously

Drug: Placebo
administered IV

Drug: Cisplatin or Carboplatin
administered intravenously
Experimental: Etoposide and Cisplatin plus Placebo Drug: OMP-59R5
OMP-59R5 administered intravenously
Other Name: Tarextumab

Drug: Etoposide
administered intravenously

Drug: Placebo
administered IV

Drug: Cisplatin or Carboplatin
administered intravenously


Outcome Measures
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Primary Outcome Measures :
  1. 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) [ Time Frame: 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.

  2. Phase 1b: Overall Response (Response Evaluable Population) [ Time Frame: 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.

  3. Phase 2: Progression Free Survival (ITT Population) [ Time Frame: 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.

  4. Phase 2: Best Overall Tumor Response Based on Investigator Assessment (ITT Population) [ Time Frame: 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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. 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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01859741


Locations
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Sponsors and Collaborators
OncoMed Pharmaceuticals, Inc.
  Study Documents (Full-Text)

Documents provided by Mereo BioPharma ( OncoMed Pharmaceuticals, Inc. ):
Statistical Analysis Plan  [PDF] March 23, 2017
Study Protocol and Informed Consent Form  [PDF] April 22, 2016

More Information
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Responsible Party: OncoMed Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01859741    
Other Study ID Numbers: 59R5-003
First Posted: May 22, 2013    Key Record Dates
Results First Posted: May 1, 2019
Last Update Posted: September 9, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Mereo BioPharma ( OncoMed Pharmaceuticals, Inc. ):
Newly diagnosed Stage IV Small Cell Lung Cancer
Additional relevant MeSH terms:
Layout table for 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
 Cisplatin
Carboplatin
Etoposide
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action