Urothelial CarcinomaPhase 2ReChiVeNCT01093066
Prospective Multicentric Evaluation of a Bladder Preservation Strategy
A Phase 2 study testing optimal TURB in people with Urothelial Carcinoma, run by Centre Hospitalier Universitaire de Saint Etienne at 31 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Urothelial Carcinoma
- What is being tested?
- optimal TURB
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- 31 sitesFrance
- Study dates
- 21 Sep 2010to 31 Dec 2020
- Phase
- Phase 2
- 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 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
31 sites in 1 country.
31 sites in 1 country
France31 sites
CH du Pays d'Aix-en-Provence
Aix-en-Provence
Clinique AXIUM - AIX EN PROVENCE
Aix-en-Provence
CHU Bordeaux
Bordeaux, 33000
Clinique Saint-Augustin
Bordeaux
Institut Bergonie
Bordeaux
CHU Caen
Caen, 14000
Crlcc Francois Baclesse
Caen, 54500
CHU Créteil
Créteil
Polyclinique Du Cotentin
Équeurdreville-Hainneville
Polyclinique de Lisieux
Lisieux
APHM - Marseille - Hôpital de la Conception
Marseille, 13 385
APHM - Marseille - Hôpital la Timone
Marseille
CRLC Marseille
Marseille
Hôpital Européen - Marseille
Marseille
Hôpitaux privés de Metz
Metz
Chu Nancy
Nancy
Crlc Nancy
Nancy
Chu Nantes
Nantes
APHP - Saint-Louis
Paris
APHP- Hôpital Tenon
Paris
CHU Poitiers
Poitiers, 86000
Chu Reims
Reims
Institut Jean Godinot - Reims
Reims
Clinique Mutualiste Chirurgicale
Saint-Etienne, 42055
CHU Saint-Etienne
Saint-Etienne
ICO - SITE Gauducheau - ICL Nantes
Saint-Herblain, 44 805
ICLN
Saint-Priest-en-Jarez, 42270
Hôpitaux du Léman - Thonon-les-Bains
Thonon-les-Bains
CHI Toulon
Toulon
CHU Toulouse
Toulouse, 31059
INSTITUT CLAUDIUS REGAUD - CRLC Toulouse
Toulouse, 31059
About this study
Official title: Prospective Multicentric Evaluation of a Bladder Preservation Strategy Using a Combination of Neoadjuvant Chemotherapy and Optimal Bladder Transurethral Resection in Patients With a Urothelial Carcinoma
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.
Read the detailed description
Every patient having signed the inform consent will have the following steps 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.
If a complete response is obtained (no tumor cells in the bladder muscle on the last TURB), a surveillance will be proposed without any further treatment.
Otherwise (tumor cells in the bladder muscle at the second TURB), a radical cystectomy will be done.
If the balder is spared, the follow up will be as follow: clinical examination, CT, bladder endoscopy and urinary cytology every 6 months. The possible non muscle infiltrative bladder relapses will be treated according
- Conditions
- Urothelial Carcinoma
- Being tested
- optimal TURB
- Keywords
- urothelial carcinoma, TURB, chemotherapy
- Medical subject headings
- Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
optimal TURBDrug
The TURB will always try to be optically complete.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: optimal TURB |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 5 years
Secondary outcomes (6)
proportion of complete response
Measured: 6 months
Chemotherapy tolerance in a neoadjuvant setting using the intensified MVAC
Measured: 3 months
Secondary cystectomy rate
Measured: 6 months
Progression free survival (either infiltrative [≥ T2] or metastatic)
Measured: 5 years
Overall bladder preservation rate
Measured: 5 years
Overall survival
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2010 (estimated)
- Study start21 Sep 2010
- Primary completion31 Dec 2020
- Study completion31 Dec 2020
Why it stopped: Difficulties in the inclusion and follow-up of patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de Saint EtienneThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 77 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicolas MOTTET, MD, Principal investigator, clinique Mutualiste chirurgicale
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01093066
- Sponsor's protocol ID
- 0908038
- Other IDs
- 2009-014264-19, 2009
- Acronym
- ReChiVe
- Status last verified
- Dec 2021
- First submitted
- 24 Mar 2010
- Last updated
- 30 Dec 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Multicentric Evaluation of a Bladder Preservation Strategy Using a Combination of Neoadjuvant Chemotherapy and Optimal Bladder Transurethral Resection in Patients With a Urothelial Carcinoma
- ClinicalTrials.gov ID
- NCT01093066
- Acronym / sponsor ID
- ReChiVe / 0908038
- Conditions
- Urothelial Carcinoma
- Keywords
- urothelial carcinoma, TURB, chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulties in the inclusion and follow-up of patients
- Enrolment
- 77 participants (estimated)
- Lead sponsor
- Centre Hospitalier Universitaire de Saint EtienneUniversity, hospital or other
- Study start
- 21 Sep 2010 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 25 Mar 2010 (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 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.
Detailed description
Every patient having signed the inform consent will have the following steps 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.
If a complete response is obtained (no tumor cells in the bladder muscle on the last TURB), a surveillance will be proposed without any further treatment.
Otherwise (tumor cells in the bladder muscle at the second TURB), a radical cystectomy will be done.
If the balder is spared, the follow up will be as follow: clinical examination, CT, bladder endoscopy and urinary cytology every 6 months. The possible non muscle infiltrative bladder relapses will be treated according
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| surgical resection and chemotherapy | Experimental | Drug: optimal TURBMaximal 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. |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- 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
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 |
|---|---|---|
| optimal TURBThe TURB will always try to be optically complete. | Drug | surgical resection and chemotherapy |
Primary outcome
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).
Time frame: 5 years
6 secondary outcomes
proportion of complete response
Time frame: 6 months
Chemotherapy tolerance in a neoadjuvant setting using the intensified MVAC
Time frame: 3 months
Secondary cystectomy rate
Time frame: 6 months
Progression free survival (either infiltrative [≥ T2] or metastatic)
Time frame: 5 years
Overall bladder preservation rate
Time frame: 5 years
Overall survival
Time frame: 5 years
Results and safety
The study was stopped early (reason given: Difficulties in the inclusion and follow-up of patients). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2021.
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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.
Nicolas MOTTET, MD principal investigator
clinique Mutualiste chirurgicale
31 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing optimal TURB in people with Urothelial Carcinoma, run by Centre Hospitalier Universitaire de Saint Etienne at 31 sites 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 3 inclusion and 4 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: stopped early, as of the sponsor's last update on 30 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early (reason given: Difficulties in the inclusion and follow-up of patients). Results are not available in the source record.
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?
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). (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Dec 2021.