A Phase II Trial Evaluating an Organ-conserving Strategy by Radiochemotherapy for Muscle-infiltrative Bladder Cancer

NCT01495676 | Terminated Results DMC

• 2 other identifiers: GETUG V042011-000408-17
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 12

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.

Conditions

Infiltrating Bladder Urothelial Carcinoma

Keywords

Bladder cancer; Organ-conserving strategy; Radiochemotherapy; non metastatic

Outcome Measures

Primary Outcomes (1)

• Disease-free Survival

  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

  Two years after the end of the complete therapeutic sequence

Secondary Outcomes (3)

• 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

Study Arms (2)

Radiotherapy + cisplatin

ACTIVE COMPARATOR

Other: Radiation + cisplatin

Radiotherapy + cisplatin + gemcitabine

EXPERIMENTAL

Other: Radiation + cisplatin + gemcitabine

Interventions

Radiation + cisplatin OTHER

RT will encompass bilateral internal and external iliac lymph nodes at a dose of 45 Gy and the bladder up to 63 Gy. Fractionation will be 1.8 Gy per fraction. Cisplatin: 20 mg/m2/day through continuous iv perfusion for 4 consecutive days, from D2 to D5 and from D23 to D26 for the first part of the treatment, then from D2 to D5 if an additional treatment is decided. A cystoscopy with a transurethral resection will be performed 3 weeks after the last day of the first part of radio-chemotherapy. * In the absence of tumor cells, the 2nd part will start on the 4th week or at latest on the 5th week after the last day of the 1st part of radio-chemotherapy. * In case of a microscopic tumor residue or of a local tumor progression, operability will be re-evaluated in view of a radical cystectomy and the patient will exit the study.

Radiotherapy + cisplatin

Radiation + cisplatin + gemcitabine OTHER

Radiotherapy will encompass bilateral internal and external iliac lymph nodes at a dose of 45 Gy and the bladder up to 63 Gy. Fractionation will be 1.8 Gy per fraction. Cisplatin: 20 mg/m2/day through continuous iv perfusion for 4 consecutive days, from D2 to D5 and from D23 to D26 for the first part of the treatment, then from D2 to D5 for the second part of the treatment if an additional treatment is decided. Gemcitabine: iv injection for 30 minutes, twice a week at a dose of 25 mg/m2 on days 2, 5, 9, 12, 16, 19, 23, 26, 30, and 33 for the 1st part of treatment, then on days 2, 5, 9, and 12 for the 2nd part of treatment if an additional treatment is decided (cystoscopy with a transurethral resection). RT will be delivered between 2 and 6 hours after completion of the gemcitabine injection.

Radiotherapy + cisplatin + gemcitabine

Eligibility Criteria

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

You may qualify if:

• 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
• No contraindication to gemcitabine or cisplatin.
• No contraindication to radiotherapy
• Information letter and informed consent signed
• Patient covered by social security

You may not qualify if:

• 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

Sponsors & Collaborators

• Institut du Cancer de Montpellier - Val d'Aurelle: lead

Study Sites (12)

Institut Bergonié

Bordeaux, 33000, France

Location

Centre Francois Baclesse

Caen, 14000, France

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

CRLC GF Leclerc

Dijon, 21000, France

Location

CRLC Val d'Aurelle-Paul Lamarque

Montpellier, 34000, France

Location

Centre azuréen de Cancérologie

Mougins, 06250, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hopital saint Louis

Paris, 75010, France

Location

HEGP

Paris, 75015, France

Location

Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, 42705, France

Location

Clinique Patseur

Toulouse, 31300, France

Location

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54511, France

Location

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MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Radiation; Cisplatin; Gemcitabine

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)

Physical Phenomena; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

no data for Measurement of Quality of Life

Results Point of Contact

• Title: Mme Aurore Moussion, Director of Direction of Clinical Research and Innovation
• Organization: INSTITUT REGIONAL DU CANCER DE MONTPELLIER

drci-icm105@icm.unicancer.fr

0467613102

Study Officials

• Azria David, MD

  ICM Val d'Aurelle

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2011
• First Posted: December 20, 2011
• Study Start: July 6, 2011
• Primary Completion: July 25, 2022
• Study Completion: December 7, 2024
• Last Updated: October 10, 2025
• Results First Posted: October 10, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (12)