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Perioperative Chemotherapy for Patients With Locally Advanced Bladder Cancer (VESPER)

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ClinicalTrials.gov Identifier: NCT01812369
Recruitment Status : Recruiting
First Posted : March 18, 2013
Last Update Posted : December 7, 2016
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Bladder Cancer Drug: GEMCITABINE CISPLATINE Drug: METHOTRXATE VINBLASTINE DOXORUBICINE CISPLATINE G-CSF Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Study Start Date : March 2013
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

Arm Intervention/treatment
Experimental: GC
gemcitabine 1250 mg/m2 D1 and D8 cisplatine 70 mg/m2 D1 each cycle every 3 weeks, 4 cycles
Drug: GEMCITABINE CISPLATINE
Active Comparator: MVAC-HD
Methotrexate 30 mg/m2 D1 Vinblastine 3 mg/m2 D2 Doxorubicine 30 mg/m2 D2 Cisplatine 70 mg/m2 D2 G-CSF D3 and D9 Each cycle every 2 weeks, 6 cycles
Drug: METHOTRXATE VINBLASTINE DOXORUBICINE CISPLATINE G-CSF



Primary Outcome Measures :
  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 Outcome Measures :
  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 ]


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01812369


Contacts
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Contact: Christian PFISTER, MD 00332888163 christian.pfister@chu-rouen.fr
Contact: Julien BLOT julien.blot@chu-rouen.fr

Locations
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France
UHRouen Recruiting
Rouen, France, 76031
Contact: Christian PFISTER, MD    00332888163    christian.fister@chu-rouen.fr   
Principal Investigator: Christian PFISTER, MD         
Sponsors and Collaborators
University Hospital, Rouen
Investigators
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Study Director: Christian PFISTER, MD CCAFU
Study Director: Stephane CULINE, MD GETUG

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Responsible Party: University Hospital, Rouen
ClinicalTrials.gov Identifier: NCT01812369     History of Changes
Other Study ID Numbers: 2011/119/HP
First Posted: March 18, 2013    Key Record Dates
Last Update Posted: December 7, 2016
Last Verified: December 2016
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Gemcitabine
Methotrexate
Doxorubicin
Liposomal doxorubicin
Vinblastine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Dermatologic Agents
Folic Acid Antagonists