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Completed

NCT Number: NCT01812369

Perioperative Chemotherapy for Patients With Locally Advanced Bladder Cancer

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.

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Key information

Conditions

Bladder Cancer Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Male Urogenital Diseases Neoplasms Neoplasms by Site Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

UHRouen

Rouen, 76031, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

GEMCITABINE CISPLATINE

Drug

METHOTRXATE VINBLASTINE DOXORUBICINE CISPLATINE G-CSF

Drug

Primary outcomes

  1. Progression-free survival (PFS) at 3 years

    Time frame: 3 years

    Evaluation of efficacy in terms of progression-free survival at 3 years of the combination of gemcitabine and cisplatin (GC) versus high dose methotrexate, vinblastine, doxorubicin and cisplatin (HD-MVAC) as perioperative chemotherapy for locally advanced -transitional cell carcinoma of the bladder.

Secondary outcomes

  1. · Toxicity (CTC AE v4.0)

    Time frame: 3 years

  2. · Response (RECIST criteria)

    Time frame: 3 years

  3. · Time to progression (TTP)

    Time frame: 3 years

  4. number of patients with adverse events ; type and grade of adverse events for each chemotherapy

    Time frame: 3 years

Sponsors and collaborators

Lead sponsor

University Hospital, Rouen

Other

Registry information

Official study title

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

Acronym: VESPER

Important dates

Study start
2013
Primary completion
2023
Study completion
2023
First posted
Mar 18, 2013
Registry last updated
Oct 6, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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