Prospective Multicentric Evaluation of a Bladder Preservation Strategy

NCT ID: NCT01093066

Last Updated: 2021-12-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-21
• Study Completion Date: 2020-12-31

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

Conditions

Urothelial Carcinoma

Keywords

urothelial carcinoma; TURB; chemotherapy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

surgical resection and chemotherapy

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.

Group Type: EXPERIMENTAL

optimal TURB

Intervention Type: DRUG

The TURB will always try to be optically complete.

Interventions

optimal TURB

The TURB will always try to be optically complete.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Saint Etienne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicolas MOTTET, MD

Role: PRINCIPAL_INVESTIGATOR

clinique Mutualiste chirurgicale

Locations

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-Etienne, , 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, , France

Countries

France

Other Identifiers

2009-014264-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

0908038

Identifier Type: -

Identifier Source: org_study_id