A Randomized Phase II Trial Evaluating an Organ-conserving Strategy With Radiotherapy + CDDP + Gemcitabine vs Radiotherapy + CDDP in Muscle-infiltrative Bladder Cancer
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Infiltrating Bladder Urothelial Carcinoma
- Sponsor
- Institut du Cancer de Montpellier - Val d'Aurelle
- Enrollment
- 69
- Locations
- 12
- Primary Endpoint
- Disease-free Survival
- Status
- Terminated
- Last Updated
- 6 months ago
Overview
Brief Summary
If radical cystectomy remains the standard of care for muscle invasive bladder cancer, consequences of this surgical procedure are often harsh. Over the past years, concurrent chemo-radiotherapy has imposed itself as an alternative treatment. Published data on concomitant radiochemotherapy (radiotherapy/cisplatin or radiotherapy/cisplatin/5-fluorouracil combinations) showed local control rates with bladder preservation at 5 years ranging from 40% to 65% according to the disease stage, and overall survival probabilities ranging from 40% to 50% at 5 years. In order to improve local and systemic prognosis, evaluation of other chemotherapy agents with higher radiosensitizing effect, such as gemcitabine, is justified. Gemcitabine possesses its own anti-cancer activities on urothelial diseases and has a synergetic activity with cisplatin. The investigators completed a monocenter phase I study combining radiotherapy, cisplatin, and twice-weekly gemcitabine, and determined a recommended dose of gemcitabine 25 mg/m². The objective of the present study is to evaluate the combination of radiotherapy + cisplatin + gemcitabine in terms of disease-free survival in non metastatic muscle invasive urothelial cancer patients.
Detailed Description
The objective of the present study is to evaluate the combination of radiotherapy + cisplatin + gemcitabine in terms of disease-free survival in non metastatic muscle invasive urothelial cancer patients.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Muscle invasive urothelial cancer (front line or following the progression of a superficial tumor), pT2-pT3 stage without lymphatic impairment (N0) and without detectable metastases (M0). An optimal macroscopic resection (TURB) have to be performed
- •The proof of invasive tumor to the muscle should be brought by a transurethral resection under anaesthesia less than 8 weeks before or, in the absence, by superficial biopsies and formal imaging. Multiples biopsies in the bladder must also be performed.
- •Age ≥ 18 years
- •Life expectancy ≥ 6 months
- •Kanorfsky index ≥ 70 % (WHO 0, 1, 2)
- •Biological criteria: neutrophils ≥ 1500/mm3, Platelets ≥ 100 000/mm3, haemoglobin ≥ 10 g/dl, creatinine clearance \> 60 ml/mn
- •No distant metastases (Thorax, abdomen, and pelvic CT-scan, bone scan)
- •Efficient contraception for premenopausal women, maintained during the whole treatment and up to two months after the completion of radiotherapy.
- •No radiotherapy or chemotherapy history except for in situ bladder lesions.
- •No carcinological history except for non melanoma skin tumours, in situ uterine cervix cancer
Exclusion Criteria
- •Bladder tumors without any muscle infiltration
- •Epidermoid carcinoma or adenocarcinoma
- •Distance metastases or extrapelvic node positivity
- •Severe digestive history (ulcerative colitis, complicated diverticulitis)
- •Pregnancy and breast feeding
Outcomes
Primary Outcomes
Disease-free Survival
Time Frame: Two years after the end of the complete therapeutic sequence
The time to relapse is defined as the time from the date of randomisation to the date of the first event. Time to relapse for patients without any event (local, regional, distance, or death) will be censored at the date of latest information. Patients without relapse and living at 2 years will be considered a success
Secondary Outcomes
- Overall Survival(Up to 5 years)
- Acute and Late Toxicities(Up to 5 years)
- Correlation Between Lymphocyte Apoptosis and Severity of Late Toxicities.(Up to 5 years)