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Brief Title: Perioperative Chemotherapy for Patients With Locally Advanced Bladder Cancer

Randomized Phase III Study of Gemcitabine/Cisplatine (GC) Versus High-dose Intensity Methotrexate, Vinblastine, Doxorubicine and Cisplatin (HD-MVAC) in the Perioperative Setting for Patients With Locally Advanced Transitional Cell Cancer of the Bladder

INTRODUCTION

  • Org Study ID: 2011/119/HP
  • Secondary ID: N/A
  • NTC ID: NCT01812369
  • Sponsor: University Hospital, Rouen

BRIEF SUMMARY


Radical cystectomy remains the gold standard treatment for invasive non metastatic
transitional cell cancer (TCC) of the bladder. In contemporary series, specific survival
rates are about 60 to 65% at 5 years, decreasing for locally advanced disease to 45-50% in
patients with nonorgan-confined lymph-node negative tumours and to 30-35% in patients with
lymph node positive tumours. Perioperative chemotherapy (adjuvant ou neoadjuvant) has been
developed in order to improve these results. Thanks to randomized trials and meta-analysis,
it can be concluded that perioperative chemotherapy increases overall survival with an
absolute benefit of 5%, equating to a survival rate of 50% at 5 years for nonorgan-confined
tumours. However, the chemotherapy administration time and the optimal chemotherapy regimen
to be delivered are not yet determined. Meta-analyses have shown that the benefit is only
observed for chemotherapy regimens including cisplatin. In daily management 4 to 6 cycles of
gemcitabine and cisplatin are delivered since this combination has been shown to yield a
similar efficacy with a better tolerance as compared to the MVAC regimen (methotrexate,
vinblastine, doxorubicin and cisplatin) in the metastatic setting. As HD-MVAC has been shown
to be associated with higher response rates than MVAC in bladder metastatic disease, also a
better efficacy of HD-MVAC can be suspected in the perioperative setting. Investigators
therefore designed a randomized phase III study to compare the efficacy of GC and HD-MVAC in
term of progression-free survival in patients for whom chemotherapy has been decided, before
or after radical cystectomy. Secondary endpoints include overall survival, side effects,
response rate in the neoadjuvant setting and ancillary studies focusing on gemcitabine and
cisplatin sensitivity. The total number of patients projected is 500. The number of patients
is based on the median progression-free survival rate of 50% at 3 years observed in patients
treated with GC (standard arm A) in the perioperative setting. An absolute improvement of 10%
(HR=0.74) is expected with HD-MVAC (experimental arm B) with a=0.05 and b=0.20. An interim
analysis is planned after the occurrence of 174 events. With an estimated uniform accrual
rate of 140 patients per year for 3.5 years and exponential survival, the final analysis is
expected to occur 8 years after the start of the trial.


  • Overall Status
    Recruiting
  • Start Date
  • Phase
    Phase 3
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Progression-free survival (PFS) at 3 years

Primary Outcome 1 - Timeframe: 3 years

CONDITION

  • Bladder Cancer

ELIGIBILITY


Inclusion Criteria:

- Primary tumour of the bladder

- Histologically confirmed infiltrating urothelial carcinoma (epidermoid and/or
glandular variants are accepted if combined with TCC)

- Disease defined by a T2, T3 or T4a N0 (lymph node £ 10 mm on CT scan) M0 stadification
for patients receiving neoadjuvant chemotherapy OR pT3 or pT4 OR pN+ whatever pT and
M0 for patients receiving adjuvant chemotherapy

- 18 ≤ age ≤ 80 years

- General condition 0 or 1 as per the WHO scale

- Absence of previous chemotherapy for muscle-invasive disease

- Haematological function: Haemoglobin > 11 g/dl, neutrophils ≥ 1500/mm3, platelets ≥
100,000/mm3

- Liver function: Grade* 0 ASAT and ALAT, grade* 0 alkaline phosphatases, normal
bilirubin

- Renal function: calculated (or measured) creatinine clearance ³ 40 ml/min - ---
Patients covered by a social security scheme

- Patient having read the information sheet and signed the informed consent form.

Exclusion Criteria:

- Pure adenocarcinoma or pure epidermoid carcinoma or mixed or pure small-cell
neuroendocrine carcinoma

- Ventricular ejection fraction < 50%

- History of cancer in the 5 years prior to entry in the trial other than basal cell
skin cancer or in situ epithelioma of the cervix

- Male or female patients not agreeing to use an effective method of contraception
throughout the duration of treatment and for 6 months after treatment discontinuation

- Pregnant women, or female subjects liable to become pregnant or currently
breast-feeding,

- Patient already included in another therapeutic trial on an investigational medicinal
product,

- Persons deprived of their freedom or under judicial protection (including
guardianship)

- Unable to receive medical follow-up during the trial owing to geographical, social or
psychological reasons.

Gender: All

Minimum Age: 80 Years

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Christian PFISTER, MD

Role: Study Director

Affiliation: CCAFU

Overall Contact

Name: Christian PFISTER, MD

Phone: 00332888163

Email: christian.pfister@chu-rouen.fr

LOCATION

Facility Status Contact
Facility: UHRouen
Rouen, 76031
France
Status: Recruiting Contact:
Christian PFISTER, MD
00332888163
christian.fister@chu-rouen.fr