Bladder Preservation or Cystectomy for MIBC

NCT07821177 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 23-409
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

In this research study, investigators will assess whether it is feasible to use information from the genes of a tumor combined with evaluation of the tumor response to systemic therapy to determine if bladder sparing chemoradiation can be used or if surgery to remove the bladder, or radical cystectomy, is needed.

Conditions

Muscle-Invasive Bladder Carcinoma; Bladder Cancer; Urothelial Carcinoma

Keywords

Muscle-Invasive Bladder Carcinoma; Bladder Cancer; MIBC; urothelial carcinoma; bladder preservation

Outcome Measures

Primary Outcomes (1)

• Feasibility Failure Rate (FFR)

  FFR defined as the proportion of participants that achieve feasibility failure. Feasibility is defined as the ability to derive interpretable information from ≥70% of evaluable patients from tumor genomics and/or transcriptomic studies before NAC plus mpMRI or cystoscopic evaluation and urine cytology to guide the patient toward an informed decision for bladder preservation chemoradiation vs. RC. Evaluable patients are those who initiate planned NAC.

  Approximately 16 weeks after initiation of neoadjuvant chemotherapy

Secondary Outcomes (8)

• Clinical Complete Response (cCR) Rate

  Approximately 16 weeks after initiation of neoadjuvant chemotherapy

• Bladder Preserving Rate

  Approximately 24 weeks after initiation of neoadjuvant chemotherapy, at time of definitive therapy

• Median Bladder-Intact Disease-Free Survival (BIDFS)

  Disease evaluated radiolagically after completion of cisplatin-based neoadjuvant chemotherapy and after definitive treatment with chemoradiation/radical cystectomy.In long-term follow-up,data collected every 3-6 months for 2 years or progressive disease.

• Recurrence Rate at 1 Year

  Relevant to this endpoint is at 1 year

• Recurrence Rate at 2 Year

  Relevant to this endpoint is at 2 year

Study Arms (2)

Arm A: Chemoradiation Therapy

EXPERIMENTAL

Participants who are 1) molecular positive after standard of care neoadjuvant therapy and have a clinical complete response, OR 2) molecular negative after standard of care neoadjuvant therapy and have a clinical complete response with ≤cT1 disease can opt for chemoradiation therapy and will complete: * Chemoradiation therapy of either: * Predetermined dose of Cisplatin 1x weekly * Predetermined dose of Gemcitabine 2x weekly * Predetermined dose of 5FU continuous infusion for days 1-5 and 16-20 in combination with predetermined dose of Mitomycin 1x on day 1 * Predetermined dose of Cisplatin and 5FU 1x daily on days 1-3, 8-10, 15-17 for the duration of radiation. * Radiation regimen per investigator discretion for 4 or 7 weeks. * CT chest and CT or MRI of abdomen and pelvis. * Follow Up Period Visits: CT chest and CT or MRI of abdomen and pelvis and cystoscopy with possible biopsy or removal of residual cancer tissue. * End of study visit.

Drug: Gemzar; Drug: Cisplatin; Drug: Adrucil; Drug: Mitomycin

Arm B: Radical Cystectomy

EXPERIMENTAL

Participants who have cT2 disease after standard of care neoadjuvant therapy will undergo standard of care RC and will complete: * Radical cystectomy * CT chest and CT or MRI of abdomen and pelvis. * Follow Up Period Visits: CT chest and CT or MRI of abdomen and pelvis and cystoscopy with possible biopsy or removal of residual cancer tissue. * Participants are eligible to receive standard of care adjuvant therapy * End of study visit.

Procedure: Radical Cystectomy

Interventions

Gemzar DRUG

Nucleoside metabolic inhibitor, 200 mg single-dose vial, via intravenous infusion per standard of care.

Arm A: Chemoradiation Therapy

Cisplatin DRUG

Platinum-based drug, 50 mg single-dose vial containing, via intravenous infusion per standard of care.

Arm A: Chemoradiation Therapy

Adrucil DRUG

Antineoplastic antimetabolite, 500 mg single-dose vial, via intravenous infusion per standard of care.

Arm A: Chemoradiation Therapy

Mitomycin DRUG

Antibiotic, single-dose vials containing either 5, 10, 20, or 40 mg of mitomycin, via intravenous infusion per standard of care.

Arm A: Chemoradiation Therapy

Radical Cystectomy PROCEDURE

Surgical removal of the bladder

Also known as: RC

Arm B: Radical Cystectomy

Eligibility Criteria

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

You may qualify if:

• Patient must have signed written informed consent indicating understanding of the purpose of the study and willingness to participate prior to any protocol-related procedures, including screening evaluation.
• Participants must have histologically confirmed cT2-cT4aN0M0 urothelial (transitional cell) carcinoma of the bladder. Mixed histology is acceptable as long as there is a majority component of urothelial carcinoma.
• Availability of baseline archival tumor tissue obtained for molecular analysis and correlative studies
• Age ≥ 18 years
• Candidate for radical cystectomy
• Cisplatin eligible
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Participants infected with human immunodeficiency virus on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• Participants with evidence of chronic hepatitis B virus infection with an undetectable HBV viral load on suppressive therapy, if indicated, are eligible for this trial
• Participants with a history of hepatitis C virus (HCV) must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Participants with a prior or concurrent history of malignancy whose natural history of treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational protocol are eligible for this trial
• Participants must have adequate organ and marrow function as defined below:
• Leukocytes ≥3,000/mcL
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count ≥1,500/mcL

You may not qualify if:

• Patients with urothelial carcinoma of the ureter, urethra, or renal pelvis
• Contraindication for bladder radiation
• Inoperable primary tumor
• Any previous systemic chemotherapy or radiotherapy for bladder cancer
• Inflammatory bowel disease
• Patients who are receiving or have received any other investigational agents within 6 months of study entry
• Child-Pugh class C hepatic impairment
• Receipt of the last dose of intravesical chemotherapy or biologic therapy ≤ 42 days (6 weeks) prior to the first dose of study drug for patients who have received prior intravesical chemotherapy or biologic therapy (e.g. BCG)
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, unstable cardiac arrhythmia, symptomatic interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
• Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions, and requirements
• Pregnant women are excluded from this study because chemotherapy and radiation have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with chemotherapy, breastfeeding should be discontinued if the mother is treated with chemotherapy.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

Gemcitabine; Cisplatin; Fluorouracil; Mitomycin; Cystectomy

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Charlene Mantia, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: September 2, 2026
• First Posted: September 15, 2026
• Study Start: September 2, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2029
• Last Updated: September 15, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)