- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04486781
A Study of Pembrolizumab+ sEphB4 in Metastatic Urothelial Carcinoma
A Phase II Trial of Pembrolizumab as Standard of Care + sEphB4-HSA in Chemotherapy Ineligible or Chemotherapy Refusing Patients With Metastatic Urothelial Carcinoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The combination of Pembrolizumab + sEphB4-HSA will be given through an intravenous infusion (into a vein). Each cycle of sEphB4-HSA will be given at Day 1, 8, and 15 of each 3 week cycle. Each cycle of Pembrolizumab will be given at Day 1 of each 3 week cycle.
Participants may continue on study protocol as long as they continue to respond and remains clinically stable on study medication.
Patients may come off treatment for the following reasons:
- Disease progression.
- If tumor resolves.
- For participants who become pregnant.
- Incidence or severity of adverse drug reaction in this or other studies indicates a potential health hazard to subjects.
- Patient withdraws consent.
- Study termination by the Sponsor.
- Participants who are non-compliant with respect to taking drugs, keeping appointments, or having tests required for the evaluation of drug safety and efficacy.
- Participant's condition renders them unacceptable for further treatment in the judgment of the investigator.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Jon Cogan, MS
- Phone Number: 323-221-7818
- Email: info@vasgene.com
Study Locations
-
-
California
-
Santa Monica, California, United States, 90403
- Recruiting
- Sarcoma Oncology Center
-
Sub-Investigator:
- Sant Chawla, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Be willing and able to provide written informed consent/assent for the trial.
- Age ≥ 18 years.
- Be treatment naïve and have advanced (metastatic or recurrent) pathologically proven urothelial carcinoma. Patients progressing more than 12 months of their last dose of platinum-based neoadjuvant or adjuvant chemotherapy are eligible.
- Have a performance status of 0 or 1 on the ECOG Performance Scale.
- Demonstrate adequate organ function as defined in Table 1., all screening labs should be performed within 10 days of treatment initiation.
- Be ineligible for chemotherapy in the assessment of the treating physician or refusing chemotherapy in frontline setting. Cisplatin ineligibility is defined as Cresatinine Clearance (CrCl) < 60cc/min, NYHA class III hear failure, grade II neuropathy and grade II hearing loss, the latter two also apply to carboplatin-based chemotherapy.
- Be approved to begin treatment with pembrolizumab per standard of care and pembrolizumab must be available to the patient. Patient must enroll on this study prior to the receiving the second dose of pembrolizumab and prior to having restaging imaging after receiving pembrolizumab. Other PD1/PDL1 antibodies are now allowed.
- Have measurable disease based on RECIST 1.1. We request an OPTIONAL core biopsy from an accessible metastatic site after a minimum of 2 cycles of treatment AND prior to progression of disease to help the investigators better understand the activity of these drugs in tumor tissue.
In addition, we request an OPTIONAL collection of any surgical specimens obtained per standard of care during the study. For instance, specimens from metastasectomy while patient is undergoing therapy on this study.
Exclusion Criteria:
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has a known history of active TB (Bacillus Tuberculosis)
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma potentially cured after surgery or prostate cancer that is under control by hormonal agents.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Treated brain metastases are allowed.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
- Has New York Heart Association (NYHA) class 3 or 4, myocardial infarction, acute coronary syndrome, diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months; or any other intercurrent medical condition that contraindicates treatment with sEphB4HSA or pembrolizumab or places the patient at undue risk for treatment related complications.
- Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
- Uncontrolled hypertension is excluded- systolic blood pressure >140mmHg or diastolic >90mmHg. Patients experiencing white coat hypertension the office, may be considered eligible if blood pressure log at home is within acceptable limits AND upon review and agreement from the Sponsor.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Combination Therapy
All study participants will receive Pembrolizumab + sEphB4-HSA through a needle in a vein in their arm for an hour in an outpatient clinic.
Pembrolizumab will be given at Day 1 of each 3 week cycle.
The study drug (sEphB4-HSA) will be given at Day 1, 8, and 15 of each 3 week cycle.
|
sEphB-HSA may prevent tumor cells from multiplying and blocks several compounds that promote the growth of blood vessels that bring nutrients to the tumor.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Estimate of the overall response rate (ORR) of the combination of Pembrolizumab + sEphB4-HSA in the patients with previously untreated advanced (metastatic or recurrent) urothelial carcinoma who are chemotherapy ineligible or who refuse chemotherapy
Time Frame: At study entry until completion (average of 60 months)
|
Objective tumor response (OR), a derived endpoint, will be based responses as coded at each evaluation.
A patient who experiences either a confirmed complete response (CR) or a confirmed partial response (PR) according to RECIST v1.1, will be classified as having experienced an objective response.
To estimate the overall response rate (ORR) of the combination of Pembrolizumab + sEphB4-HSA in this population of patients, the number of patients who experience a confirmed complete response (CR) or a confirmed partial response (PR) will be divided by the number of eligible patients who began treatment.
|
At study entry until completion (average of 60 months)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To estimate the progression free survival (PFS) in these patients
Time Frame: Day 1, 8, 15 (each 3 week cycle), 30 days after last dose (safety follow-up), every 6 weeks (follow-up), every 12 weeks (survival follow-up) (average of 60 months)
|
Toxicity as assessed by CTCAE v5 will be documented in all eligible patients who begin treatment.
|
Day 1, 8, 15 (each 3 week cycle), 30 days after last dose (safety follow-up), every 6 weeks (follow-up), every 12 weeks (survival follow-up) (average of 60 months)
|
To estimate the overall survival (OS) in these patients
Time Frame: Baseline, Day 1, 8, 15 (each 3 week cycle), 30 days after last dose (safety follow-up), every 6 weeks (follow-up), every 12 weeks (survival follow-up) (average of 60 months)
|
Overall survival (OS) is calculated as the time from start of protocol treatment until death from any cause.
Patients who are alive at the time of analysis will be censored at the last date that they were documented alive.
OS will summarized for all eligible patients who begin treatment.
|
Baseline, Day 1, 8, 15 (each 3 week cycle), 30 days after last dose (safety follow-up), every 6 weeks (follow-up), every 12 weeks (survival follow-up) (average of 60 months)
|
To determine the tolerbility of the combination of Pembrolizumab + sEphB4-HSA in patients with previously untreated advanced urothelial carcinoma is more effective than the single agent pembrolizumab.
Time Frame: Day 1, 8, and 15 of each 3 week cycle
|
Progression-free survival (PFS) is calculated as the time from start of protocol treatment until documentation of disease progression (as defined by RECIST v1.1) or until death from any cause, whichever comes first.
Patients who are alive and have not progressed at the time of analysis will be censored at the last date that they were documented alive and free of progression.
In addition, patients who begin another treatment (i.e.
other than Pembrolizumab or sEphB4-HSA alone) prior to progressing, will be censored at the time of the start of the other treatment for the primary analysis of this endpoint.
|
Day 1, 8, and 15 of each 3 week cycle
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- UC-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Metastatic Urothelial Carcinoma
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingMetastatic Bladder Urothelial Carcinoma | Metastatic Renal Pelvis Urothelial Carcinoma | Metastatic Ureter Urothelial Carcinoma | Metastatic Urethral Urothelial Carcinoma | Metastatic Urothelial Carcinoma | Locally Advanced Bladder Urothelial Carcinoma | Locally Advanced Renal Pelvis Urothelial... and other conditionsUnited States
-
Roswell Park Cancer InstituteIovance Biotherapeutics, Inc.WithdrawnMetastatic Bladder Urothelial Carcinoma | Metastatic Renal Pelvis Urothelial Carcinoma | Metastatic Ureter Urothelial Carcinoma | Metastatic Urethral Urothelial Carcinoma | Unresectable Renal Pelvis Urothelial Carcinoma | Unresectable Ureter Urothelial CarcinomaUnited States
-
National Cancer Institute (NCI)Active, not recruitingMetastatic Bladder Urothelial Carcinoma | Metastatic Ureter Urothelial Carcinoma | Stage IV Bladder Urothelial Carcinoma AJCC v7 | Metastatic Renal Pelvis and Ureter Urothelial CarcinomaUnited States
-
University of UtahNational Cancer Institute (NCI)RecruitingMetastatic Urothelial Carcinoma | Locally Advanced Urothelial Carcinoma | Unresectable Urothelial Carcinoma | Infiltrating Urothelial Carcinoma, Sarcomatoid VariantUnited States
-
Mamta ParikhNational Cancer Institute (NCI); Karyopharm Therapeutics IncRecruitingMetastatic Urothelial Carcinoma | Locally Advanced Urothelial Carcinoma | Advanced Urothelial Carcinoma | Refractory Urothelial CarcinomaUnited States
-
National Cancer Institute (NCI)CompletedMetastatic Prostate Carcinoma | Metastatic Bladder Urothelial Carcinoma | Metastatic Renal Pelvis Urothelial Carcinoma | Metastatic Ureter Urothelial Carcinoma | Metastatic Urethral Urothelial Carcinoma | Metastatic Urothelial Carcinoma | Stage IV Bladder Urothelial Carcinoma AJCC v7 | Stage IV Renal... and other conditionsUnited States, Puerto Rico
-
Emory UniversityNational Cancer Institute (NCI); ExelixisRecruitingMetastatic Urothelial Carcinoma | Locally Advanced Urothelial Carcinoma | Unresectable Urothelial Carcinoma | Infiltrating Bladder Urothelial Carcinoma With Squamous DifferentiationUnited States
-
Emory UniversityNational Cancer Institute (NCI)RecruitingMetastatic Bladder Urothelial Carcinoma | Metastatic Renal Pelvis Urothelial Carcinoma | Metastatic Ureter Urothelial Carcinoma | Metastatic Urethral Urothelial Carcinoma | Metastatic Urothelial Carcinoma | Stage IV Bladder Cancer AJCC v8 | Stage IV Renal Pelvis Cancer AJCC v8 | Stage IV Ureter Cancer... and other conditionsUnited States
-
Shanghai Miracogen Inc.RecruitingMetastatic Urothelial Carcinoma | Locally Advanced Urothelial CancerChina
-
Incyte CorporationTerminatedMetastatic Urothelial Carcinoma | Unresectable Urothelial CarcinomaSpain, France, United States, Italy, Japan, Ireland, Slovakia, Austria, Belgium, Canada, Finland, Germany, Poland, Portugal, Romania, United Kingdom
Clinical Trials on Pembrolizumab + sEphB4-HSA
-
Vasgene Therapeutics, IncRecruiting
-
Northwestern UniversityNational Cancer Institute (NCI); Vasgene Therapeutics, IncActive, not recruitingProgressive Disease | Castration-Resistant Prostate Carcinoma | Stage IVB Prostate Cancer AJCC v8 | PSA Progression | Metastatic Prostate Adenocarcinoma | Castration Levels of Testosterone | Prostate Carcinoma Metastatic in the Bone | Castration-Resistant Prostate Carcinoma Refractory to Second-Generation... and other conditionsUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)WithdrawnRecurrent Bladder Carcinoma | Bladder Cancer Stage 0 | Bladder Cancer Stage IUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)Active, not recruitingStage IIIA Non-Small Cell Lung Cancer | Stage IIIB Non-Small Cell Lung Cancer | Head and Neck Squamous Cell Carcinoma | Recurrent Head and Neck Carcinoma | Recurrent Non-Small Cell Lung Carcinoma | Stage IV Non-Small Cell Lung Cancer | ALK Gene Mutation | EGFR Gene Mutation | Metastatic Head and Neck... and other conditionsUnited States
-
AIDS Malignancy ConsortiumNational Cancer Institute (NCI); University of Arkansas; The Emmes Company, LLC; Vasgene Therapeutics, IncRecruiting
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedStage III Renal Cell Cancer | Recurrent Bladder Carcinoma | Stage I Prostate Cancer | Stage III Prostate Cancer | Infiltrating Bladder Urothelial Carcinoma | Stage II Bladder Urothelial Carcinoma | Stage IIA Prostate Cancer | Stage IIB Prostate Cancer | Stage I Renal Cell Cancer | Stage II Renal Cell CancerUnited States
-
University of Colorado, DenverVasgene Therapeutics, IncCompletedSquamous Cell Carcinoma of Head and NeckUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI); Vasgene Therapeutics, Inc; The V Foundation...TerminatedUnspecified Adult Solid Tumor, Protocol SpecificUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)RecruitingProstate Cancer | Urothelial Carcinoma | Stage IV Bladder Urothelial CarcinomaUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedAcute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome | Chronic Myelomonocytic Leukemia | Previously Treated Myelodysplastic Syndrome | Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes | Recurrent Adult Acute Myeloid LeukemiaUnited States