TerminatedNCT02145390Updated Aug 28, 2018Results posted

Chemoradiation for Bladder Preservation After Complete Response to Neoadjuvant Chemotherapy

An interventional study of Transurethral Resection of the Bladder Tumor & Cystoscopy and Intensity Modulated Radiation Therapy in Bladder Cancer, Bladder Carcinoma and Transition Cell Cancer, sponsored by University of Miami. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-08-28.

Sponsored by University of Miami · Not applicable, Interventional, and Treatment

Why this study was terminated

Investigator Decision - Insufficient Accrual

Phase: Not applicable
Study type: Interventional
Enrollment: 1
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study 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.

Read the detailed description

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.
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;
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
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
For subjects with pT1 or worse tumor response to neoadjuvant chemotherapy: Radical Cystectomy within 12 weeks after post-neoadjuvant evaluation;
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.

Conditions studied

Bladder Cancer
Bladder Carcinoma
Transition Cell Cancer
Muscle Invasive Bladder Carcinoma

Browse trials for

Urinary Bladder Neoplasms 1,649

Keywords

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

In context

Urinary Bladder Neoplasms

1,649 studies on the registry are indexed under Urinary Bladder Neoplasms; 427 are open to participants now.

This study's enrollment of 1 is below the median of 60 across 1,183 interventional studies indexed under Urinary Bladder Neoplasms.

Browse Urinary Bladder Neoplasms studies →

Lead sponsor

University of Miami is the lead sponsor of 838 studies on the registry; 164 are open to participants now.

Of its 114 completed or terminated interventional studies of FDA-regulated products, 96 (84%) have results posted.

Browse University of Miami studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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.)
Note: Prechemotherapy laboratory investigations and Eastern Cooperative Oncology Group (ECOG) evaluation must meet inclusion criteria irrespective of where they were drawn, retroactive, prior to cycle 1 of cisplatin/gemcitabine. Inclusion criteria from these initial investigations will be used for evaluation of enrollment eligibility.
Patients must be willing and able to provide study-specific informed consent prior to study entry

Exclusion criteria

Exclusion Criteria:

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)
Pregnancy or women of childbearing potential [not post-menopausal or permanently sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy)] and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
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

Study design

Phase: Not applicable
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 1 participant (actual)

Study arms

Experimental
TURBT, NAC and Chemoradiation
* 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

ProcedureTransurethral Resection of the Bladder Tumor & Cystoscopy
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
RadiationIntensity Modulated Radiation Therapy
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
BehavioralExpanded Prostate Cancer Index Composite Short Form 12
Quality of life questionnaire to be administered to subjects at intervals defined by the study protocol.
Also known as: EPIC SF-12
BehavioralInternational Prostate Symptom Score
Quality of life questionnaire to be administered to subjects at intervals defined by the study protocol.
Also known as: IPSS

What researchers measure

Primary outcomes

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.
Time frame: 2 years

Secondary outcomes

Rate of Failure-Free Survival (FFS) at Two Years
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.
Time frame: 2 Years
Rate of Acute and Late Grade 2 or Higher Treatment-Related GU, GI and Hematologic Toxicity.
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.
Time frame: Up to 2 years Post-Treatment
Rate of Overall Survival 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.
Time frame: Up to 3 years

Other outcomes

Evaluation of Known Predictive and Prognostics Biomarkers for Complete Response to Neoadjuvant Chemotherapy and Bladder Preservation.
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.
Time frame: Up to 1 year Post-Treatment, About 2 years
Identification of New Predictive and Prognostic Biomarkers for Response to Neoadjuvant Chemotherapy, and Bladder Preservation.
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.
Time frame: Up to 1 year Post-Treatment, About 2 years

Results

Posted Aug 28, 2018

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.

Participant flow

Participant flow — Overall Study
Milestone	TURBT, NAC and Chemoradiation
Started	1
Completed	0
Not completed	1
Withdrew: Withdrawal by subject	1

Outcome measures

PrimaryRate 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.

Time frame:: 2 years