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

NCT ID: NCT01495676

Last Updated: 2025-10-10

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

69 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-07-06

Study Completion Date

2024-12-07

Brief Summary

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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

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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

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Infiltrating Bladder Urothelial Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Radiotherapy + cisplatin

Group Type ACTIVE_COMPARATOR

Radiation + cisplatin

Intervention Type 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 + gemcitabine

Group Type EXPERIMENTAL

Radiation + cisplatin + gemcitabine

Intervention Type 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.

Interventions

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Radiation + cisplatin

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.

Intervention Type OTHER

Radiation + cisplatin + gemcitabine

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.

Intervention Type OTHER

Eligibility Criteria

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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institut du Cancer de Montpellier - Val d'Aurelle

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Azria David, MD

Role: STUDY_CHAIR

ICM Val d'Aurelle

Locations

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Institut Bergonié

Bordeaux, , France

Site Status

Centre Francois Baclesse

Caen, , France

Site Status

Hopital Henri Mondor

Créteil, , France

Site Status

CRLC GF Leclerc

Dijon, , France

Site Status

CRLC Val d'Aurelle-Paul Lamarque

Montpellier, , France

Site Status

Centre azuréen de Cancérologie

Mougins, , France

Site Status

Centre Antoine Lacassagne

Nice, , France

Site Status

Hopital saint Louis

Paris, , France

Site Status

HEGP

Paris, , France

Site Status

Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, , France

Site Status

Clinique Patseur

Toulouse, , France

Site Status

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Site Status

Countries

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France

References

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Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2011-000408-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GETUG V04

Identifier Type: -

Identifier Source: org_study_id

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