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Using gemcitabine and cisplatin to treat muscle invasive bladder cancer with specific genetic changes

A Phase II Study of Gemcitabine Plus Cisplatin Chemotherapy in Patients With Muscle-invasive Bladder Cancer With Bladder Preservation for Those Patients Whose Tumors Harbor Deleterious DNA Damage Response (DDR) Gene Alterations

PHASE2 · Alliance for Clinical Trials in Oncology · NCT03609216

This study is testing if a combination of two chemotherapy drugs can help people with muscle invasive bladder cancer that has certain genetic changes live longer and feel better.

Quick facts

PhasePHASE2
Study typeInterventional
Enrollment271 (estimated)
Ages18 Years and up
SexAll
SponsorAlliance for Clinical Trials in Oncology (other)
Drugs / interventionschemotherapy, immunotherapy, radiation
Locations414 sites (Fairbanks, Alaska and 413 other locations)
Trial IDNCT03609216 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effectiveness of gemcitabine hydrochloride and cisplatin in treating patients with muscle invasive bladder urothelial cancer that has specific deleterious DNA damage response (DDR) gene alterations. The study aims to determine the three-year event-free survival rate, clinical response rate, and overall survival for patients receiving this chemotherapy regimen. Participants will be monitored for their response to treatment and the potential need for radical cystectomy. The trial also evaluates the local treatment burden and bladder-intact disease-free survival in different patient groups.

Who should consider this trial

Good fit: Ideal candidates are patients with histologically confirmed muscle-invasive urothelial carcinoma of the bladder and specific genetic alterations.

Not a fit: Patients with non-invasive bladder cancer or those with multifocal carcinoma in situ may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment approach could provide a bladder-sparing option for patients with muscle invasive bladder cancer, potentially improving their quality of life.

How similar studies have performed: Other studies have shown promise with similar chemotherapy approaches in bladder cancer, but this specific focus on DDR gene alterations is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Step 1 Patient Registration Eligibility Criteria
* Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided the extent of disease is confirmed via imaging and/or examination under anesthesia (EUA). The diagnostic TURBT sample must have been obtained within 60 days prior to registration
* 20 unstained slides (10 micron thickness) of formalin-fixed paraffin-embedded (FFPE) pre-treatment diagnostic transurethral resection (TUR) specimen available (for sequencing), with 2 (5 micron) slides at the start and end of the 20 slides, for a total of 22 unstained slides. An FFPE block is also acceptable
* Clinical stage T2-T4aN0/xM0 disease
* Medically appropriate candidate for radical cystectomy as assessed by surgeon
* No concomitant multifocal carcinoma in situ; a single focus is allowed
* A single muscle-invasive bladder tumor measuring ≤5 cm in size as defined by the surgeons at cystoscopic evaluation. When documented, pathologic size at cystoscopy and TURBT will take precedence over radiographic measurements of tumor size.
* No clinical or radiographic evidence for locally advanced or metastatic disease
* No prior anti-PD-1 or anti PD-L1 therapies, or systemic chemotherapy within the past 5 years (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x6 doses and maintenance therapy); BCG refractory disease, defined as disease recurrence within 3 months of BCG therapy, is not allowed. Intravesical chemotherapy is allowed.
* No prior radiation therapy to the bladder or prostate
* No major surgery or radiation therapy =\< 4 weeks of registration (TURBT is allowed).
* Not pregnant and not nursing. This study involves an agent that has known genotoxic, mutagenic and teratogenic effects. For women of childbearing potential only, a negative pregnancy test done =\< 14 days prior to registration is required
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Absolute neutrophil count (ANC) \>= 1,000/mm\^3
* Platelet count \>= 100,000/mm\^3
* Calculated creatinine clearance ≥ 55 mL/min using formula per institutional standard or investigator's discretion. The same formula should be used to calculate all subsequent creatinine clearances.
* Total bilirubin =\< 1.5 x upper limit of normal (ULN)

  \* (For patients with documented Gilbert's syndrome Total Bilirubin =\< 3 x ULN)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x ULN
* Alkaline phosphatase =\< 2.5 x ULN
* No evidence of New York Heart Association (NYHA) functional class III or IV heart disease
* No ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade \>= 2
* No pre-existing sensory grade \>= 2 neuropathy
* No pre-existing grade \>= 2 hearing loss
* No serious intercurrent medical or psychiatric illness, including serious active infection
* None of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
* No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the drugs used in this trial. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy, when indicated
* No history of allergic reaction attributed to compounds of similar chemical or biologic composition to the agents used in this study
* No concurrent treatment on another clinical trial; supportive care trials or non-therapeutic trials (e.g., quality of life) are allowed
* No prior malignancy except for: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible
* Step 2 Patient Registration Eligibility Criteria
* Patients must have completed 4 or more cycles of protocol-directed chemotherapy and DDR gene results must be available
* Step 3 Patient Registration Eligibility Criteria (only patients with a DDR gene alteration)
* Deleterious alteration within 1 or more of 9 pre-defined DDR genes within the pre-treatment TURBT deoxyribonucleic acid (DNA)
* Cystoscopy and imaging performed to determine stage/treatment assignment

Where this trial is running

Fairbanks, Alaska and 413 other locations

+364 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Infiltrating Bladder Urothelial Carcinoma, Stage II Bladder Urothelial Carcinoma, Stage III Bladder Urothelial Carcinoma

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.