Prospective Multicentric Evaluation of a Bladder Preservation Strategy

NCT01093066 | Terminated Phase 2 DMC

• 2 other identifiers: 09080382009-014264-19
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 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.

Conditions

Urothelial Carcinoma

Keywords

urothelial carcinoma; TURB; chemotherapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• proportion of complete response

  6 months

• Chemotherapy tolerance in a neoadjuvant setting using the intensified MVAC

  3 months

• Secondary cystectomy rate

  6 months

• Progression free survival (either infiltrative [≥ T2] or metastatic)

  5 years

• Overall bladder preservation rate

  5 years

Study Arms (1)

surgical resection and chemotherapy

EXPERIMENTAL

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.

Drug: optimal TURB

Interventions

optimal TURB DRUG

The TURB will always try to be optically complete.

surgical resection and chemotherapy

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead

Study Sites (31)

CH du Pays d'Aix-en-Provence

Aix-en-Provence, France

Location

Clinique AXIUM - AIX EN PROVENCE

Aix-en-Provence, France

Location

CHU Bordeaux

Bordeaux, 33000, France

Location

Clinique Saint-Augustin

Bordeaux, France

Location

Institut Bergonie

Bordeaux, France

Location

CHU Caen

Caen, 14000, France

Location

Crlcc Francois Baclesse

Caen, 54500, France

Location

CHU Créteil

Créteil, France

Location

Polyclinique Du Cotentin

Équeurdreville-Hainneville, France

Location

Polyclinique de Lisieux

Lisieux, France

Location

APHM - Marseille - Hôpital de la Conception

Marseille, 13 385, France

Location

APHM - Marseille - Hôpital la Timone

Marseille, France

Location

CRLC Marseille

Marseille, France

Location

Hôpital Européen - Marseille

Marseille, France

Location

Hôpitaux privés de Metz

Metz, France

Location

Chu Nancy

Nancy, France

Location

Crlc Nancy

Nancy, France

Location

Chu Nantes

Nantes, France

Location

APHP - Saint-Louis

Paris, France

Location

APHP- Hôpital Tenon

Paris, France

Location

CHU Poitiers

Poitiers, 86000, France

Location

Chu Reims

Reims, France

Location

Institut Jean Godinot - Reims

Reims, France

Location

Clinique Mutualiste Chirurgicale

Saint-Etienne, 42055, France

Location

CHU Saint-Etienne

Saint-Etienne, France

Location

ICO - SITE Gauducheau - ICL Nantes

Saint-Herblain, 44 805, France

Location

ICLN

Saint-Priest-en-Jarez, 42270, France

Location

Hôpitaux du Léman - Thonon-les-Bains

Thonon-les-Bains, France

Location

CHI Toulon

Toulon, France

Location

CHU Toulouse

Toulouse, 31059, France

Location

INSTITUT CLAUDIUS REGAUD - CRLC Toulouse

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Nicolas MOTTET, MD

  clinique Mutualiste chirurgicale

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2010
• First Posted: March 25, 2010
• Study Start: September 21, 2010
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: December 30, 2021

Record last verified: 2021-12

Locations

FR (31)