Clinical trial NCT01093066: Prospective Multicentric Evaluation of a Bladder Preservation Strategy
Official title: Prospective Multicentric Evaluation of a Bladder Preservation Strategy Using a Combination of Neoadjuvant Chemotherapy and Optimal Bladder Transurethral Resection in Patients With a Urothelial Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Urothelial Carcinoma
Keywords: urothelial carcinoma
TURB
chemotherapy
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
First posted: 2010-03-25
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Radical cystectomy is the treatment of choice for bladder infiltrative urothelium carcinoma. But the removal of the bladder reservoir has a major impact of the Quality of life. Neoadjuvant chemotherapy has been shown to be associated with an absolute 5% survival benefit. Two monocentric studies suggest that this neoadjuvant chemotherapy could be used in combination with an optimal transurethral bladder resection, in a strategy of bladder preservation, provided a complete response being obtained (about 50% in every trial using neoadjuvant MVAC protocol before a radical cystectomy). In those both studies with patients T2 to T4, the 5 years overall survival is above 65%, with more than 40% bladder preservation rate at 5 years.

The feasibility and the efficacy of such an attitude in a multicentric trail using the most active regimen (in term of complete response in metastatic patients) is unknown. The chosen regimen is therefore the intensified MVAC which allows, with the use of G-CSF, to double the dose-intensity of Adriamycin and Cisplatinum, and to decrease by 30% the methotrexate and vinblastine dose-intensity.

The efficacy and safety confirmation of such an approach could lead to consider it in patients motivated to retain a functional bladder.

Detailed description: Every patient having signed the inform consent will have the following steps Maximal and optimal TURB using a standardized procedure. The TURB will always try to be optically complete.

Neoadjuvant chemotherapy for 3 months with the intensified MVAC (6 cycles administered every 2 weeks): METHOREXATE: 30 mg/m2 D1 - VINBLASTINE: 3 mg/m2 D2 - ADRIAMYCINE 30 mg/m2 D2 - CISPLATINE 70 mg/m2 D2. + G-CSF: 5 µg/kg from D4 to D10 New maximal standardized TURB at the end of the chemotherapy. In case of a lesion localized at the bladder dome, and if a maximal TURB appears to be unsafe, a partial cystectomy without lymph node dissection will be performed.

If a complete response is obtained (no tumor cells in the bladder muscle on the last TURB), a surveillance will be proposed without any further treatment.

Otherwise (tumor cells in the bladder muscle at the second TURB), a radical cystectomy will be done.

If the balder is spared, the follow up will be as follow: clinical examination, CT, bladder endoscopy and urinary cytology every 6 months. The possible non muscle infiltrative bladder relapses will be treated according

Eligibility criteria: Inclusion Criteria:

* T2 clinical stage (no palpable mass under anesthesia after TURB) Absence of diffuse Cis (Cis on random bladder biopsies) Patients above 18, and below 70 years of age PS status ≤ 2 No previous treatment for a bladder muscle infiltrative carcinoma. Previous endovesical instillations for non muscle infiltrative lesions (pTa, pT1, Cis) are allowed.

No metastases on tauraco-abdomina-pelvic CT scan (no node \> 1 cm) and bone scan.

Normal biological values: neutrophils \> 1,5.109 /l, platelets \> 100. 109 /l, Alkaline Phosphatases \< 2 x N, bilirubin \< 1,5 N, Transaminases \< 1,5 x N, Creatinine clearance ≥ 60 ml/min Signed inform consent Patient belonging to a social security system.

Exclusion Criteria:

All other histology than urothelial carcinoma:

* primitive adenocarcinoma
* epidermoid carcinoma
* little cells carcinoma In situ diffuse carcinoma associated with urothelial carcinoma muscular infiltrating Tumor stade \> T2, T3 or T4 or pT4a (prostatitis) Serious cardiac, pulmonary, hepatitic, renal, digestive or neurological pathology which is non equilibrating or potential aggravating risk by treatment Cancer history or other actual cancer (except skin cancer) not remission or with an end of treatment inferior to 2 years Participation to another clinical trial in a delay inferior to 30 days

Primary outcomes:
measure: the 5 years bladder preservation rate (with or without intravesical non muscle infiltrative recurrences, treated by TURB only or intravesical instillations of either BCG or mytomicin C).
timeFrame: 5 years
Secondary outcomes:
measure: proportion of complete response
timeFrame: 6 months
measure: Chemotherapy tolerance in a neoadjuvant setting using the intensified MVAC
timeFrame: 3 months
measure: Secondary cystectomy rate
timeFrame: 6 months
measure: Progression free survival (either infiltrative [≥ T2] or metastatic)
timeFrame: 5 years
measure: Overall bladder preservation rate
timeFrame: 5 years
measure: Overall survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Aix-en-Provence
country: France
facility: CH du Pays d'Aix-en-Provence
city: Aix-en-Provence
country: France
facility: Clinique AXIUM - AIX EN PROVENCE
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Bordeaux
country: France
facility: Clinique Saint-Augustin
city: Bordeaux
country: France
facility: Institut Bergonie
city: Caen
country: France
facility: CHU Caen
city: Caen
country: France
facility: Crlcc Francois Baclesse
city: Créteil
country: France
facility: CHU Créteil
city: Lisieux
country: France
facility: Polyclinique de Lisieux
city: Marseille
country: France
facility: APHM - Marseille - Hôpital de la Conception
city: Marseille
country: France
facility: APHM - Marseille - Hôpital la Timone
city: Marseille
country: France
facility: CRLC Marseille
city: Marseille
country: France
facility: Hôpital Européen - Marseille
city: Metz
country: France
facility: Hôpitaux privés de Metz
city: Nancy
country: France
facility: Chu Nancy
city: Nancy
country: France
facility: Crlc Nancy
city: Nantes
country: France
facility: Chu Nantes
city: Paris
country: France
facility: APHP - Saint-Louis
city: Paris
country: France
facility: APHP- Hôpital Tenon
city: Poitiers
country: France
facility: CHU Poitiers
city: Reims
country: France
facility: Chu Reims
city: Reims
country: France
facility: Institut Jean Godinot - Reims
city: Saint-etienne
country: France
facility: Clinique Mutualiste Chirurgicale
city: Saint-Herblain
country: France
facility: ICO - SITE Gauducheau - ICL Nantes
city: Saint-priest En Jarez
country: France
facility: ICLN
city: Saint-Étienne
country: France
facility: CHU Saint-Etienne
city: Thonon-les-Bains
country: France
facility: Hôpitaux du Léman - Thonon-les-Bains
city: Toulon
country: France
facility: CHI Toulon
city: Toulouse
country: France
facility: CHU Toulouse
city: Toulouse
country: France
facility: INSTITUT CLAUDIUS REGAUD - CRLC Toulouse
city: Équeurdreville-Hainneville
country: France
facility: Polyclinique Du Cotentin
Study officials:
affiliation: clinique Mutualiste chirurgicale
name: Nicolas MOTTET, MD
role: PRINCIPAL_INVESTIGATOR
References: