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

Stage IV Small Cell Lung Cancer Clinical Trial

— PINNACLE  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01859741
• Other study ID #: 59R5-003
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: January 7, 2012
• Est. completion date: May 8, 2017

Study information

• Verified date: September 2020
• Source: Mereo BioPharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 172
• Est. completion date: May 8, 2017
• Est. primary completion date: April 18, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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)

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Carcinoma
• Stage IV Small Cell Lung Cancer

Intervention

Drug:
• OMP-59R5
OMP-59R5 administered intravenously
• Etoposide
administered intravenously
• Placebo
administered IV
• Cisplatin or Carboplatin
administered intravenously

Locations

Country	Name	City	State
United States	University of Michigan Medical Center, Clinical Trials Office	Ann Arbor	Michigan
United States	Georgia Cancer Specialists, PC	Atlanta	Georgia
United States	Piedmont Cancer Institute	Atlanta	Georgia
United States	Texas Oncology-South Austin	Austin	Texas
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	University of Maryland, Greenebaum Cancer Center	Baltimore	Maryland
United States	Weinberg Cancer Institute	Baltimore	Maryland
United States	Texas Oncology-Bedford	Bedford	Texas
United States	Oncology and Hematology Associates of Southwest Virginia Inc.	Blacksburg	Virginia
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Tennessee Oncology, PLLC	Chattanooga	Tennessee
United States	Univeristy of Chicago Medical Center	Chicago	Illinois
United States	Oncology Hematology Care, Inc.	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Texas Oncology, P.A.	Dallas	Texas
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Sarah Cannon	Fort Myers	Florida
United States	Greenville Health System, Clinical Research Unit, Institute for Translational Oncology Research	Greenville	South Carolina
United States	The University of Texas MD A nderson Cancer Center	Houston	Texas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Minnesota Oncology Hematology , P.A.	Minneapolis	Minnesota
United States	The Sarah Cannon Research Institute	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Ocala Oncology Center, PL	Ocala	Florida
United States	Oncology Hematology West PC, dba Nebraska Cancer Specialists	Omaha	Nebraska
United States	UPMC Cancer Pavilion	Pittsburgh	Pennsylvania
United States	Providence Cancer Center Oncology and Hematology Care Eastside	Portland	Oregon
United States	Highlands Oncology Group	Rogers	Arkansas
United States	Cancer Care Network of South Texas	San Antonio	Texas
United States	Swedish Cancer Institute	Seattle	Washington
United States	Georgetown University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
OncoMed Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	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