Prospective Multicentric Evaluation of a Bladder Preservation Strategy

Urothelial Carcinoma Clinical Trial

— ReChiVe  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01093066
• Other study ID #: 0908038
• Secondary ID: 2009-014264-19
• Status: Terminated
• Phase: Phase 2
• Start date: September 21, 2010
• Est. completion date: December 31, 2020

Study information

• Verified date: December 2021
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 77
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Intervention

Drug:
• optimal TURB
The TURB will always try to be optically complete.

Locations

Country	Name	City	State
France	CH du Pays d'Aix-en-Provence	Aix-en-Provence
France	Clinique AXIUM - AIX EN PROVENCE	Aix-en-Provence
France	CHU Bordeaux	Bordeaux
France	Clinique Saint-Augustin	Bordeaux
France	Institut Bergonie	Bordeaux
France	CHU Caen	Caen
France	Crlcc Francois Baclesse	Caen
France	CHU Créteil	Créteil
France	Polyclinique Du Cotentin	Équeurdreville-Hainneville
France	Polyclinique de Lisieux	Lisieux
France	APHM - Marseille - Hôpital de la Conception	Marseille
France	APHM - Marseille - Hôpital la Timone	Marseille
France	CRLC Marseille	Marseille
France	Hôpital Européen - Marseille	Marseille
France	Hôpitaux privés de Metz	Metz
France	Chu Nancy	Nancy
France	Crlc Nancy	Nancy
France	Chu Nantes	Nantes
France	APHP - Saint-Louis	Paris
France	APHP- Hôpital Tenon	Paris
France	CHU Poitiers	Poitiers
France	Chu Reims	Reims
France	Institut Jean Godinot - Reims	Reims
France	Clinique Mutualiste Chirurgicale	Saint-etienne
France	CHU Saint-Etienne	Saint-Étienne
France	ICO - SITE Gauducheau - ICL Nantes	Saint-Herblain
France	ICLN	Saint-priest En Jarez
France	Hôpitaux du Léman - Thonon-les-Bains	Thonon-les-Bains
France	CHI Toulon	Toulon
France	CHU Toulouse	Toulouse
France	INSTITUT CLAUDIUS REGAUD - CRLC Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).		5 years
Secondary	proportion of complete response		6 months
Secondary	Chemotherapy tolerance in a neoadjuvant setting using the intensified MVAC		3 months
Secondary	Secondary cystectomy rate		6 months
Secondary	Progression free survival (either infiltrative [= T2] or metastatic)		5 years
Secondary	Overall bladder preservation rate		5 years
Secondary	Overall survival		5 years