Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Urinary Bladder Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Central Nervous System Depressants

Gemcitabine

Anesthetics

Cisplatin

* Transurethral Resection of the Bladder Tumor \& Cystoscopy (TURBT);
* Neoadjuvant Chemotherapy (NAC), per standard of care: Cisplatin and Gemcitabine therapy, within 8 weeks following the TURBT and cystoscopic evaluation;
* For subjects with complete response (CR): Chemoradiation within 6 weeks after post-neoadjuvant evaluation. Intensity Modulated Radiation Therapy (IMRT/VMAT); Cisplatin therapy per standard of care;
* For subjects who have pT1 or worse tumor response: Radical Cystectomy, per standard of care, within 12 weeks post-neoadjuvant chemotherapy evaluation;
* Expanded Prostate Cancer Index Composite Short Form 12 (EPIC SF-12);
* International Prostate Symptom Score (IPSS).

TURBT and Cystoscopy will be performed by the participating urologist prior to start of neoadjuvant chemotherapy, per the study protocol:

* Cystoscopic evaluation
* Bimanual examination under anesthesia,
* Transurethral resection of the bladder tumor,
* Biopsy of the prostatic urethra including both mucosa and stroma using a resection loop.

Transurethral Resection of the Bladder Tumor & Cystoscopy

For subjects with complete response to neoadjuvant chemotherapy. Subjects will receive 25 daily fractions (5 weeks) of radiation therapy for 5 days a week (Monday to Friday) except on weekends or holidays, when remaining fractions will be added to the end of treatment. The overall schema is for IMRT based radiation to the entire bladder, prostate (in men) and the pelvic lymph nodes:

* Pelvic lymph nodes: 45 Gy in 25 fractions at 1.8 Gy per fraction.
* Whole bladder and prostate: 50 Gy in 25 fractions at 2.0 Gy per fraction.
* Tumor boost area: 60-65 Gy in 25 fractions at 2.4-2.6 Gy per day
* Final boost dose will be determined at the discretion of the treating physician based on normal tissue exposure and volume.

Intensity Modulated Radiation Therapy

Quality of life questionnaire to be administered to subjects at intervals defined by the study protocol.

Expanded Prostate Cancer Index Composite Short Form 12

International Prostate Symptom Score

Adrian S Ishkanian, MD

Bladder preservation in patients with complete response after neoadjuvant chemotherapy will lead to equivalent or superior relapse free rates compared to cystectomy rates from historical controls.

1. Transurethral Resection of the Bladder Tumor (TURBT) and Cystoscopy performed by participating urologist:

   * cystoscopic evaluation
   * bimanual examination under anesthesia,
   * as thorough as possible a transurethral resection (TUR) of the bladder tumor,
   * and a biopsy of the prostatic urethra including both mucosa and stroma using a resection loop.
2. Neoadjuvant Chemotherapy, per standard of care: All patients will receive the neoadjuvant course of chemotherapy. The recommended neoadjuvant chemotherapy regimen consists of Gemcitabine and Cisplatin given on a 21-day cycle.This regimen will begin within 8 weeks following the TURBT and cystoscopic evaluation by the urologic surgeon;
3. Post-Neoadjuvant Evaluation: This evaluation will take place ≤ 6 weeks following the completion of the neoadjuvant chemotherapy. Evaluation will include:

   * urine cytology,
   * cystoscopy,
   * tumor site transurethral biopsy,
   * and bimanual examination after biopsy
   * and biopsy of TURBT site
4. For subjects with complete response to neoadjuvant chemotherapy: Chemoradiation within 6 weeks after post-neoadjuvant evaluation. Intensity Modulated Radiation Therapy (IMRT/VMAT), and concurrent Cisplatin therapy, per standard of care; OR
5. For subjects with pT1 or worse tumor response to neoadjuvant chemotherapy: Radical Cystectomy within 12 weeks after post-neoadjuvant evaluation;
6. Post-Consolidation Endoscopic Evaluations: The first post-treatment evaluation will be 30 days +/- 14 days within the end of chemoradiation, surgery or at progression. Subsequent cystoscopic evaluation will be every three months in the first year, every four months in the second year, and every six months in the third year (all evaluations to occur +/- 14 days). Each evaluation will include serum, plasma, whole blood, urine cytology.

Chemoradiation for Bladder Preservation After Complete Response to Neoadjuvant Chemotherapy

A Phase II Study of Chemoradiation for Bladder Preservation in Patients With Muscle Invasive Bladder Carcinoma After Complete Response to Neoadjuvant Chemotherapy

To evaluate known predictive and prognostic biomarkers for complete response to neoadjuvant chemotherapy and bladder preservation. Blood, urine and tumor tissue will be collected pre- and post-neoadjuvant chemotherapy, post-cystectomy or chemoradiation, and at any time point of distant metastases.

To perform exploratory molecular analysis to identify new predictive and prognostic biomarkers for response to neoadjuvant chemotherapy, and bladder preservation. Blood, urine and tumor tissue for muscle invasive bladder cancer. Blood, urine and tumor tissue will be collected pre and post-neoadjuvant chemotherapy, post-cystectomy or chemoradiation, and at any time point of distant metastases.

Rate of failure free survival with intact bladder (FFSIB) at two years in subjects undergoing bladder preservation. FFSIB is defined by the absence of any failures (locoregional, distant metastasis, and death) and bladder preservation (no radical cystectomy for any causes) after definitive chemoradiation. FFSIB is defined as the time elapsed from the start of neoadjuvant chemotherapy to the date of documented failure events or radical cystectomy. For failure-free patients (without failure events and no radical cystectomy), FFSIB will be censored at the last date of documented failure-free bladder preservation (FFBP) status.

The two year rate of failure free survival (FFS) in study participants. This will include locoregional recurrence, and distant metastases. FFS is defined as absence of any failures (locoregional, distant metastasis, and death) during the time elapsed from the start of neoadjuvant chemotherapy to the date of documented failure events or radical cystectomy.

The rate of acute and late grade 2 or higher (CTCAE v4.0) treatment-related genitourinary (GU), gastrointestinal (GI) and hematologic toxicity of bladder preservation in study participants.

Rate of Overall Survival in Study Participants. Overall survival (OS) is defined as the time elapsed from the start of neoadjuvant chemotherapy until death. Surviving patients (including patients lost to follow up) will be censored at the date of last contact.

University of Miami

Assistant Professor

TURBT, NAC and Chemoradiation

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

A minimum of 35 evaluable participants were required for the analysis of data for the study outcome measures. Fewer than the minimum number of participants required were enrolled therefore data were not analyzed.

Adrian Ishkanian MD

A minimum of 35 evaluable participants were required for the analysis of this outcome measure. Fewer than 35 participants were enrolled therefore data were not analyzed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Chemoradiation for Bladder Preservation After Complete Response to Neoadjuvant Chemotherapy	NCT02145390	Bladder Cancer Bladder Carcino... Transition Cell... Muscle Invasive...	Transurethral R... Intensity Modul... Expanded Prosta... International P...	18 Years -	University of Miami
Chemoradiation for Bladder Preservation After Complete Response to Neoadjuvant Chemotherapy	NCT02145390	Bladder Cancer Bladder Carcino... Transition Cell... Muscle Invasive...	Transurethral R... Intensity Modul... Expanded Prosta... International P...	18 Years -	University of Miami

Spots Global Cancer Trial Database for international prostate symptom score