Combination Therapy With Pembrolizumab and sEphB4-HSA in Previously Treated Urothelial Carcinoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02717156|
Recruitment Status : Recruiting
First Posted : March 23, 2016
Last Update Posted : May 30, 2018
|Condition or disease||Intervention/treatment||Phase|
|Stage IV Bladder Urothelial Carcinoma||Procedure: Computed Tomography Other: Laboratory Biomarker Analysis Biological: Pembrolizumab Procedure: Positron Emission Tomography Biological: Recombinant EphB4-HSA Fusion Protein||Phase 2|
I. To determine the feasibility of using pembrolizumab-recombinant EphB4-HSA fusion protein (sEphB4-HSA) combination in patients with advanced urothelial carcinoma.
II. To measure the overall survival (OS).
I. To measure the progression-free survival (PFS). II. To measure the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
I. To examine programmed cell death 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), programmed cell death 1 ligand 2 (PD-L2) and EPH receptor B4 (EphB4) expression by tumor cells (TC) as well as immune cells (IC)- macrophages and T cells- in tumor tissue and correlate them with ORR, PFS and OS.
II. To examine the tumor tissue T cell frequency (counts), tumor tissue T cell clonality using T cell receptor (TCR) sequencing, and peripheral blood T cell clonality, pre-treatment and post-treatment and correlate these with ORR, PFS and OS.
III. To measure the phenotype of lymphocytes and myeloid derived suppressor cells (MDSC), in pre and post-treatment blood samples and correlate these with ORR, PFS and OS; an extra blood sample for future studies will also be collected and banked.
IV. To examine peripheral blood circulating tumor cells (CTCs) for enumeration and molecular analysis in pre and post-treatment blood samples, and correlate these with ORR, PFS and OS.
V. To collect and bank tumor tissue. VI. To examine the role of adding positron emission tomography (PET) to a contrast computed tomography (CT) for evaluation of response to treatment.
Patients receive recombinant EphB4-HSA fusion protein intravenously (IV) over 60 minutes on days 1, 8, and 15 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 6-12 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of sEphB4-HSA in Combination With Anti PD1 Antibody Pembrolizumab (MK-7435) for Metastatic Urothelial Cancer Refractory to Platinum|
|Actual Study Start Date :||November 21, 2016|
|Estimated Primary Completion Date :||November 21, 2019|
|Estimated Study Completion Date :||November 21, 2020|
Experimental: Treatment (EphB4-HSA and pembrolizumab)
Patients receive recombinant EphB4-HSA fusion protein IV over 60 minutes on days 1, 8, and 15 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Procedure: Computed Tomography
Other: Laboratory Biomarker Analysis
Procedure: Positron Emission Tomography
Biological: Recombinant EphB4-HSA Fusion Protein
Other Name: sEphB4-HSA
- Incidence of toxicities and adverse events classified according to the Common Terminology Criteria for Adverse Events v4.03 [ Time Frame: Up to 30 days ]All observed toxicities will be summarized in terms of type (organ affected or laboratory determination, severity, and time of onset. Tables will be created to summarize these toxicities and side effects, overall and by course. The proportion of patients who are eligible to begin the 3rd planned cycle will be calculated, using the number of eligible patients who began treatment as the denominator; 95% confidence intervals will be constructed.
- OR defined as complete response or partial response according to RECIST v 1.1 [ Time Frame: Up to 3 years ]The proportion of patients who experience an overall objective response (CR or PR will be calculated as the ratio of the number of eligible patients who experienced the response, divided by the total number of eligible patients who began treatment; 95% confidence intervals will be constructed.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02717156
|Contact: Cheryl Kefauver, RN||323-865-0459||Cheryl.Kefauver@med.usc.edu|
|United States, California|
|City of Hope||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Valerie Mira 626-218-0171 email@example.com|
|Contact: Tina Moore 626-218-5282 firstname.lastname@example.org|
|Principal Investigator: Tanya Dorff, MD|
|USC / Norris Comprehensive Cancer Center||Recruiting|
|Los Angeles, California, United States, 90033|
|Contact: Sarmad Sadeghi 323-865-0553 email@example.com|
|Principal Investigator: Sarmad Sadeghi|
|Principal Investigator:||Sarmad Sadeghi, MD||University of Southern California|