Prospective Multicentric Evaluation of a Bladder Preservation Strategy
Conditions
Urothelial Carcinoma
Conditions: official terms
Carcinoma - Carcinoma, Transitional Cell
Conditions: Keywords
urothelial carcinoma, TURB, chemotherapy
Study Type
Interventional
Study Phase
Phase 2
Study Design
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: optimal TURB
Type: Procedure
Overall Status
Recruiting
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
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 69 Years
Minimum Age: 18 Years
Gender: Both
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
Locations
RAVAUD Alain
Bordeaux, France
Status: Recruiting
Contact: Alain RAVAUD, MD - alain.ravaud@chu-bordeaux.fr
Henri BENSADOUN
Caen, France
Status: Recruiting
Contact: Henri BENSADOUN, Dr
Eric LECHEVALLIER
Marseille, France
Status: Recruiting
Contact: Eric LECHEVALLIER, Dr - elechevallier@ap-hm.fr
RIGAUD Jérôme
Nantes, France
Status: Recruiting
Contact: Jérôme RIGAUD, Dr - jrigaud@chu-nantes.fr
IRANI Jacques
Poitiers, France
Status: Recruiting
Contact: Jacques IRANI, Dr - j.irani@chu-poitiers.fr
Clinique Mutualiste Chirurgicale
Saint-etienne, France
Status: Recruiting
Contact: Nicolas MOTTET, Dr - nmottet@mutualite-loire.com
BOMPAS Emmanuelle
Saint-herblain, France
Status: Recruiting
Contact: Emmanuelle BOMPAS, MD - e-bompas@nantes.fnclcc.fr
GUILLOT Aline
Saint-priest En Jarez, France
Status: Recruiting
Contact: Aline GUILLOT, MD - aline.guillot@icloire.fr
CHEVREAU Christine
Toulouse, France
Status: Recruiting
Contact: Christine CHEVREAU, MD
SOULIE Michel
Toulouse, France
Status: Recruiting
Contact: Michel SOULIE - soulie.m@chu-toulouse.fr
GEOFFROY Lionel
Vandoeuvre Les Nancy, France
Status: Recruiting
Contact: Lionel GEOFFROY, MD - l.geoffrois@nancy.fnclcc.fr
Start Date
September 2010
Completion Date
December 2022
Sponsors
Centre Hospitalier Universitaire de Saint Etienne
Source
Centre Hospitalier Universitaire de Saint Etienne
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page