Brief Title
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
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
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
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).
Secondary Outcome
proportion of complete response
Condition
Urothelial Carcinoma
Intervention
optimal TURB
Study Arms / Comparison Groups
surgical resection and chemotherapy
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
77
Start Date
September 21, 2010
Completion Date
December 2022
Primary Completion Date
December 2022
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
Gender
All
Ages
18 Years - 69 Years
Accepts Healthy Volunteers
No
Contacts
Nicolas MOTTET, MD, ,
Location Countries
France
Location Countries
France
Administrative Informations
NCT ID
NCT01093066
Organization ID
0908038
Secondary IDs
2009-014264-19
Responsible Party
Sponsor
Study Sponsor
Centre Hospitalier Universitaire de Saint Etienne
Study Sponsor
Nicolas MOTTET, MD, Principal Investigator, clinique Mutualiste chirurgicale
Verification Date
December 2020