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) (PINNACLE)

Study Description

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Brief Summary:

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 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

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	145 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 :	May 2013
Actual Primary Completion Date :	May 8, 2017
Actual Study Completion Date :	May 8, 2017

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; 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; Drug: Etoposide; administered intravenously; Drug: Placebo; administered IV; Drug: Cisplatin or Carboplatin; administered intravenously

Outcome Measures

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Primary Outcome Measures :

1. 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) ]
   The maximum tolerated dose (MTD) will be determined in patients treated with OMP-59R5 in combination with etoposide and cisplatin
2. Progression-free survival [ Time Frame: Number of days from randomization until death or disease progression, assessed up 25 months ]
   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 :

1. 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 ]
   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.
2. Overall survival, 12 month OS and overall response rate [ Time Frame: Throughout the study, and approximately every 6 weeks after the treatment termination ]
   Survival status, anti-cancer treatment during the survival follow-up after the treatment termination, overall response at each tumor assessment
3. 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 ]
   AEs, laboratory assessment and physical examination.

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. 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

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Sponsors and Collaborators

OncoMed Pharmaceuticals, Inc.

More Information

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Responsible Party:	OncoMed Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT01859741 History of Changes
Other Study ID Numbers:	59R5-003
First Posted:	May 22, 2013
Last Update Posted:	April 4, 2018
Last Verified:	April 2018

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	Carboplatin; Etoposide; Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Physiological Effects of Drugs