Bladder CancerPhase 3VESPERNCT01812369
Perioperative Chemotherapy for Patients With Locally Advanced Bladder Cancer
A Phase 3 study testing GEMCITABINE CISPLATINE and METHOTRXATE VINBLASTINE DOXORUBICINE CISPLATINE G-CSF in people with Bladder Cancer, run by University Hospital, Rouen at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Bladder Cancer
- What is being tested?
- GEMCITABINE CISPLATINE and METHOTRXATE VINBLASTINE DOXORUBICINE CISPLATINE G-CSF
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 1 siteFrance
- Study dates
- Feb 2013to 25 Sep 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- Bladder Cancer
- Being tested
- GEMCITABINE CISPLATINE, METHOTRXATE VINBLASTINE DOXORUBICINE CISPLATINE G-CSF
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GEMCITABINE CISPLATINEDrug
METHOTRXATE VINBLASTINE DOXORUBICINE CISPLATINE G-CSFDrug
| Study group | Role | What they receive |
|---|---|---|
| GC | Experimental | gemcitabine 1250 mg/m2 D1 and D8 cisplatine 70 mg/m2 D1 each cycle every 3 weeks, 4 cycles Receives: Drug: GEMCITABINE CISPLATINE |
| MVAC-HD | Active comparator | 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 Receives: Drug: METHOTRXATE VINBLASTINE DOXORUBICINE CISPLATINE G-CSF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS) at 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.
Measured: 3 years
Secondary outcomes (4)
· Toxicity (CTC AE v4.0)
Measured: 3 years
· Response (RECIST criteria)
Measured: 3 years
· Time to progression (TTP)
Measured: 3 years
number of patients with adverse events ; type and grade of adverse events for each chemotherapy
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2013 (estimated)
- Study startFeb 2013
- Primary completion25 Sep 2023
- Study completion25 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by University Hospital, RouenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 500 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christian PFISTER, MD, Study director, CCAFUStephane CULINE, MD, Study director, GETUG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01812369
- Sponsor's protocol ID
- 2011/119/HP
- Acronym
- VESPER
- Status last verified
- Oct 2025
- First submitted
- 22 Jan 2013
- Last updated
- 6 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Pfister C, Harter V, Fontugne J, Allory Y, Culine S; VESPER Trial Investigators. Prognostic Factors for Overall Survival in the VESPER Trial: Basal Molecular Subtype Is a Relevant Key Factor. Eur Urol Oncol. 2026 Jan 22:S2588-9311(26)00004-0. doi: 10.1016/j.euo.2026.01.003. Online ahead of print.
PubMed 41577609Pfister C, Gravis G, Flechon A, Chevreau C, Mahammedi H, Laguerre B, Guillot A, Joly F, Soulie M, Allory Y, Harter V, Culine S; VESPER Trial Investigators. Perioperative dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin in muscle-invasive bladder cancer (VESPER): survival endpoints at 5 years in an open-label, randomised, phase 3 study. Lancet Oncol. 2024 Feb;25(2):255-264. doi: 10.1016/S1470-2045(23)00587-9. Epub 2023 Dec 21.
PubMed 38142702Pfister C, Gravis G, Flechon A, Chevreau C, Mahammedi H, Laguerre B, Guillot A, Joly F, Soulie M, Allory Y, Harter V, Culine S; VESPER Trial Investigators. Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients With Nonmetastatic Muscle-Invasive Bladder Cancer: Results of the GETUG-AFU V05 VESPER Trial. J Clin Oncol. 2022 Jun 20;40(18):2013-2022. doi: 10.1200/JCO.21.02051. Epub 2022 Mar 7.
PubMed 35254888
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01812369
- Acronym / sponsor ID
- VESPER / 2011/119/HP
- Conditions
- Bladder Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 500 participants (actual)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Study start
- Feb 2013 (actual)
- Primary completion
- 25 Sep 2023 (actual)
- Study completion
- 25 Sep 2023 (actual)
- First posted
- 18 Mar 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GC | Experimental | Drug: GEMCITABINE CISPLATINEgemcitabine 1250 mg/m2 D1 and D8 cisplatine 70 mg/m2 D1 each cycle every 3 weeks, 4 cycles |
| MVAC-HD | Active comparator | Drug: METHOTRXATE VINBLASTINE DOXORUBICINE CISPLATINE G-CSFMethotrexate 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 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (8 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GEMCITABINE CISPLATINE | Drug | GC |
| METHOTRXATE VINBLASTINE DOXORUBICINE CISPLATINE G-CSF | Drug | MVAC-HD |
Primary outcome
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.
4 secondary outcomes
· Toxicity (CTC AE v4.0)
Time frame: 3 years
· Response (RECIST criteria)
Time frame: 3 years
· Time to progression (TTP)
Time frame: 3 years
number of patients with adverse events ; type and grade of adverse events for each chemotherapy
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2025.
- Derived from this study: PubMed 41577609Pfister C, Harter V, Fontugne J, Allory Y, Culine S; VESPER Trial Investigators. Prognostic Factors for Overall Survival in the VESPER Trial: Basal Molecular Subtype Is a Relevant Key Factor. Eur Urol Oncol. 2026 Jan 22:S2588-9311(26)00004-0. doi: 10.1016/j.euo.2026.01.003. Online ahead of print.
- Derived from this study: PubMed 38142702Pfister C, Gravis G, Flechon A, Chevreau C, Mahammedi H, Laguerre B, Guillot A, Joly F, Soulie M, Allory Y, Harter V, Culine S; VESPER Trial Investigators. Perioperative dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin in muscle-invasive bladder cancer (VESPER): survival endpoints at 5 years in an open-label, randomised, phase 3 study. Lancet Oncol. 2024 Feb;25(2):255-264. doi: 10.1016/S1470-2045(23)00587-9. Epub 2023 Dec 21.
- Derived from this study: PubMed 35254888Pfister C, Gravis G, Flechon A, Chevreau C, Mahammedi H, Laguerre B, Guillot A, Joly F, Soulie M, Allory Y, Harter V, Culine S; VESPER Trial Investigators. Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients With Nonmetastatic Muscle-Invasive Bladder Cancer: Results of the GETUG-AFU V05 VESPER Trial. J Clin Oncol. 2022 Jun 20;40(18):2013-2022. doi: 10.1200/JCO.21.02051. Epub 2022 Mar 7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christian PFISTER, MD study director
CCAFU
Stephane CULINE, MD study director
GETUG
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing GEMCITABINE CISPLATINE and METHOTRXATE VINBLASTINE DOXORUBICINE CISPLATINE G-CSF in people with Bladder Cancer, run by University Hospital, Rouen at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) at 3 years (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01812369, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2025.