Chemoradiation for Bladder Preservation After Complete Response to Neoadjuvant Chemotherapy

NCT02145390 | Terminated Results DMC

• 1 other identifier: 20130896
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bladder Cancer; Bladder Carcinoma; Transition Cell Cancer; Muscle Invasive Bladder Carcinoma

Keywords

Bladder Cancer; Bladder Carcinoma; Transition Cell Cancer; TCC; Muscle Invasive Bladder Carcinoma

Outcome Measures

Primary Outcomes (1)

• Rate of Failure-Free Survival With Intact Bladder (FFSIB) in Study Participants

  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.

  2 years

Secondary Outcomes (3)

• Rate of Failure-Free Survival (FFS) at Two Years

  2 Years

• Rate of Acute and Late Grade 2 or Higher Treatment-Related GU, GI and Hematologic Toxicity.

  Up to 2 years Post-Treatment

• Rate of Overall Survival in Study Participants

  Up to 3 years

Other Outcomes (2)

• Evaluation of Known Predictive and Prognostics Biomarkers for Complete Response to Neoadjuvant Chemotherapy and Bladder Preservation.

  Up to 1 year Post-Treatment, About 2 years

• Identification of New Predictive and Prognostic Biomarkers for Response to Neoadjuvant Chemotherapy, and Bladder Preservation.

  Up to 1 year Post-Treatment, About 2 years

Study Arms (1)

TURBT, NAC and Chemoradiation

EXPERIMENTAL

* 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).

Procedure: Transurethral Resection of the Bladder Tumor & Cystoscopy; Radiation: Intensity Modulated Radiation Therapy; Behavioral: Expanded Prostate Cancer Index Composite Short Form 12; Behavioral: International Prostate Symptom Score

Interventions

Transurethral Resection of the Bladder Tumor & Cystoscopy PROCEDURE

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.

Also known as: TURBT

TURBT, NAC and Chemoradiation

Intensity Modulated Radiation Therapy RADIATION

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.

Also known as: IMRT, VMAT

TURBT, NAC and Chemoradiation

Expanded Prostate Cancer Index Composite Short Form 12 BEHAVIORAL

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

Also known as: EPIC SF-12

TURBT, NAC and Chemoradiation

International Prostate Symptom Score BEHAVIORAL

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

Also known as: IPSS

TURBT, NAC and Chemoradiation

Eligibility Criteria

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

You may qualify if:

• Pathologically proven diagnosis of primary carcinoma of the bladder(transitional cell cancer). Must be operable patients with muscularis propria invasion and American Joint Committee on Cancer (AJCC) clinical stages T2-4a, N0 or N+, M0. Patients with prostatic urethra involvement with transitional cell cancer (TCC) are eligible if it is completely resected and the patient has no evidence of stromal invasion of the prostate.
• Patients must be able to tolerate systemic chemotherapy combined with pelvic radiation therapy and radical cystectomy.
• Zubrod Performance Status of ≤1.
• Age ≥18.
• Complete Blood Count (CBC)/differential obtained no more than 8 weeks prior to enrollment on study, with adequate bone marrow function defined as follows:
• White Blood Cell (WBC) ≥ 4000/ml
• Absolute neutrophil count (ANC) ≥1,800 cells/mm
• Platelets ≥100,000 cells/mm
• Hemoglobin ≥ 10.0 mg/dl (Note: the use of transfusion or other intervention to achieve this level is acceptable)
• Serum bilirubin of 2.0mg or less;
• Serum creatinine of 1.5mg or less; creatinine clearance of 60ml/min or greater no more than 8 weeks prior to enrollment (Note: calculated creatinine clearance is permissible, using Cockcroft-Gault formula. If the creatinine clearance is greater than 60ml/min, then a serum creatinine of up to 1.8mg is allowable at the discretion of the principal investigator.)
• Patients must be willing and able to provide study-specific informed consent prior to study entry

You may not qualify if:

• Tumor related untreated active hydronephrosis
• Evidence of distant metastases.
• Diffuse bladder carcinoma in situ (CIS) not able to be encompassed in a boost radiotherapy volume.
• Previous systemic chemotherapy (for any cancer) or pelvic radiation therapy
• A prior or concurrent malignancy of any other site or histology unless the patient has been disease free for greater than or equal to five years except for non-melanoma skin cancer and/or stage T1a prostate cancer or carcinoma in situ of the uterine cervix
• Patients that are not candidates for radical cystectomy (T4b disease are considered unresectable)
• Severe active co-morbidity:
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
• Transmural myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of enrollment
• History of hepatic insufficiency resulting in clinical jaundice and/or coagulation defects (Note: laboratory tests for liver function and coagulation parameters are not required for enrollment into this protocol)
• Known diagnosis of Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition (Note: HIV testing is not required for enrollment into this protocol). The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
• As determined by the investigator or principal investigator

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Cystoscopy; Radiotherapy, Intensity-Modulated

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

Intervention Hierarchy (Ancestors)

Endoscopy; Diagnostic Techniques, Surgical; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Urological; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Urologic Surgical Procedures; Urogenital Surgical Procedures; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Limitations and Caveats

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.

Results Point of Contact

• Title: Adrian Ishkanian MD
• Organization: University of Miami

aishkanian@miami.edu

305-243-4200

Study Officials

• Adrian S Ishkanian, MD

  University of Miami Sylvester Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 20, 2014
• First Posted: May 22, 2014
• Study Start: January 5, 2016
• Primary Completion: April 25, 2017
• Study Completion: April 25, 2017
• Last Updated: August 28, 2018
• Results First Posted: August 28, 2018

Record last verified: 2018-08

Locations

US (1)