Pembrolizumab (MK3475), Gemcitabine, and Concurrent Hypofractionated Radiation Therapy for Muscle-Invasive Urothelial Cancer of the Bladder

NCT02621151 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 15-00220
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 5

Brief Summary

This trial is to assess the efficacy of pembrolizumab (MK3475) added to concurrent radiation and gemcitabine in the management of patients with muscle-invasive urothelial cancer who are not candidates for or decline radical cystectomy.

Conditions

Muscle-invasive Urothelial Cancer of the Bladder

Keywords

combination therapy; immunotherapy; immune checkpoint inhibition

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved Two-year Bladder-intact Disease-free Survival

  Bladder-intact disease-free survival is defined as the time from initiation of protocol therapy until the first occurrence of muscle-invasive bladder cancer recurrence, regional pelvic recurrence, distant metastases, bladder cancer-related death, or cystectomy.

  2 years

Secondary Outcomes (3)

• Complete Response (CR) Rate

  up to 21 weeks

• Percentage of Participants Who Survived at Study Completion

  up to 5 years

• Percentage of Participants Who Achieved Metastasis-free Survival at Study Completion

  up to 5 years

Study Arms (1)

Pembrolizumab, Gemcitabine, and RT

EXPERIMENTAL

* Lead-in single dose Pembrolizumab 200 mg, intravenously (IV) * Transurethral Resection of Bladder Tumor (TURBT) at pre-RT (maximal) and completion of therapy (diagnostic) * External Beam Radiation Therapy (EBRT) - 52 Gy in 20 fractions over 4 weeks (1 fraction = 2.6 Gy) * Gemcitabine 27 mg/m\^2 IV twice weekly for 4 weeks concurrent with EBRT * Pembrolizumab 200 mg IV every 3 weeks for total 3 doses starting day 1 of EBRT

Biological: Pembrolizumab; Procedure: Transurethral Resection of Bladder Tumor; Drug: Gemcitabine; Radiation: External Beam Radiation Therapy

Interventions

Pembrolizumab BIOLOGICAL

Also known as: MK3475, Keytruda

Pembrolizumab, Gemcitabine, and RT

Transurethral Resection of Bladder Tumor PROCEDURE

Pembrolizumab, Gemcitabine, and RT

Gemcitabine DRUG

Also known as: Gemzar

Pembrolizumab, Gemcitabine, and RT

External Beam Radiation Therapy RADIATION

Pembrolizumab, Gemcitabine, and RT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed muscle-invasive urothelial cancer of the bladder within 60 days of study enrollment. Patients must be willing to provide a TURBT specimen during screening and prior to enrollment if adequate specimen (FFPE tissue block or 20 unstained slides) from initial TURBT documenting muscle-invasive urothelial bladder cancer is not available.
• Clinical stage T2-T4a, N0, M0 urothelial bladder cancer.
• Deemed to not be a candidate for radical cystectomy by attending urologic oncologist or refuse radical cystectomy.
• Be willing and able to provide written informed consent/assent for the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group Performance Scale.
• Demonstrate adequate organ function as defined below, all screening labs should be performed within 10 days of protocol enrollment.
• Absolute neutrophil count \>= 1,500 /mcL;
• Platelets \>= 100,000 /mcL;
• Hemoglobin \>= 9.0 g/dL;
• Serum creatinine \<=1.5 x upper limit of normal (ULN) or calculated creatinine clearance \>= 30 mL/min as calculated by Cockcrof-Gault formaulae or by 24 hour urine collection;
• Serum total bilirubin \<=1.5 x ULN or direct bilirubin \<= ULN for subjects with total bilirubin levels \> 1.5 x ULN;
• Aspartate aminotransferase and alanine aminotransferase \<= 1.5 x ULN;
• Albumin \>= 2.5 mg/dL;
• International normalized ratio or prothrombin time (PT) \<= 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial prothrombin time (PTT) is within therapeutic range of intended use of anticoagulants;

You may not qualify if:

• Has received prior targeted small molecule therapy, radiation therapy or systemic chemotherapy for urothelial bladder cancer including neoadjuvant chemotherapy. Prior intravesical chemotherapy or intravesical immunotherapy is permissible, however, no prior intravesical therapy is permitted within 4 weeks of study enrollment; adjuvant therapy is not permitted.
• Has received prior pelvic radiation therapy.
• Has a history of inflammatory bowel disease or history of scleroderma.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• 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 a known history of active TB (Bacillus Tuberculosis).
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Any prior history of invasive malignancy within the past 5 years except non-melanoma skin cancer, carcinoma in-situ, localized prostate cancer without biochemical recurrence following definitive treatment.
• Has any history of inflammatory bowel disease or scleroderma.
• Has other 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.
• History of Guillain-Barre Syndrome or Stevens-Johnson Syndrome
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• NYU Langone Health: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

NYU Perlmutter Cancer Center

New York, New York, 10016, United States

Location

Memorial Sloan Kettering

New York, New York, 10065, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599-7305, United States

Location

MeSH Terms

Interventions

pembrolizumab; Transurethral Resection of Bladder; Gemcitabine

Intervention Hierarchy (Ancestors)

Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Minas Economides, MD
• Organization: NYU Langone Health

minas.economides@nyulangone.org

2127315413

Study Officials

• Minas Economides, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2015
• First Posted: December 3, 2015
• Study Start: August 11, 2016
• Primary Completion: November 10, 2022
• Study Completion: December 1, 2025
• Last Updated: October 7, 2025
• Results First Posted: October 7, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: The investigator who proposed to use the data will be granted access upon reasonable request. Requests should be directed to minas.economides@nyulangone.org. To gain access, data requestors will need to sign a data access agreement. This instance of data sharing will also require separate IRB review as well as review from NYU Langone's DSSB.

Locations

US (5)