Patients With High-risk MIBCBladder-ARTNCT03333356
Adjuvant Radiotherapy in Patients With Pathological High-risk Bladder Cancer (GETUG-AFU 30)
A study testing pelvic radiotherapy in people with Patients With High-risk MIBC, run by UNICANCER at 17 sites in France.
Trial summary
This is a randomized multicentre study in patients with high-risk MIBC to investigate adjuvant radiotherapy after radical cystectomy and pelvic lymph node dissection. The objective of the study is to provide evidence that adjuvant radiotherapy improves loco-regional control with potential benefits in survival. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Patients With High-risk MIBC
- What is being tested?
- pelvic radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 17 sitesFrance
- Study dates
- 19 Apr 2018to Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be eligible, the patients must fulfil all of the following inclusion criteria:
- Patients with histologically-confirmed muscle-invasive bladder cancer, either with pure urothelial carcinomas, or dominant urothelial carcinomas (>50%) combined with other histological variants including: micropapillary, epidermoid, or adenocarcinomas, are eligible. Patients with small cell variants, pure adenocarcinomas, or pure epidermoid carcinomas are not eligible.
- Patients with radical cystectomy and pelvic lymph nodes dissection with no microscopic residual disease (R0 and R1).
- Note that only R1 patients without urinary diversion as orthotropic neo-bladder replacement are eligible for the study, to limit cystectomy bed radiation induced toxicities.
- Patients with tumours of TNM staging: pN0-2, M0 by imagery, and pT3a, pT3b, pT4a, and pT4b, as well as, pTX-pN1-2, pTX-NX-R1 are eligible.
- Patients having received neo-adjuvant or adjuvant chemotherapy treatment are eligible. Randomization is allowed only if AE due to chemotherapy are ≤grade 2 at randomization.
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- Patients ≥18 years old.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
- Absolute neutrophil count (ANC) ≥1500 cells/mm³.
- Platelets ≥100000 cells/mm³.
- Haemoglobin ≥8 g/dL (Note: following a blood transfusion or another intervention if required).
- Adequate hepatic function: aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤2.5 x upper limit of normal (ULN); or ≤3.5 x ULN in the case of concurrent disease with known etiology and for which a corrective treatment is possible.
- Adequate renal function: clearance >30 mL/min (MDRD).
- Patients having provided written informed consent prior to any study-related procedures.
- Patients affiliated to the social security scheme.
- Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
Who cannot join
- Patient must not be enrolled if he/she fulfils any of the following non-inclusion criteria:
- Patients with R1 resection and with orthotropic neo-bladder reconstruction as urinary diversion are not eligible.
- Patients with clinical or radiological evidence of metastases or N3 staged bladder cancer are not eligible.
- Prior invasive solid tumours or haematological malignancies unless disease free for a minimum of 3 years prior to randomisation except:
- skin basal cell carcinoma,
- in situ epithelioma of the cervix,
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- or prostate cancer: incidentally discovered during cystoprostatectomy and pelvic lymph node dissection and with a good prognosis (T stage <pT3b and/or Gleason <8 and pN- and/or post-operative prostate-specific antigen (PSA) <0.1 nanogram/mL),
- Prior pelvic radiotherapy.
- Patients with active inflammatory bowel disease.
- Patients who required surgical treatment for bowel obstruction before bladder cancer diagnosis or after cystectomy.
- Prior chemotherapy for other malignant diseases within the previous 5 years, except for neoadjuvant pre-cystectomy chemotherapy or adjuvant chemotherapy which are permitted.
- Patients with the following severe acute co-morbidity are not eligible:
- Unstable angina or congestive heart failure that required hospitalization in the 6 months before randomisation.
- Transmural myocardial infarction in the 6 months prior to randomisation.
- Acute bacterial or fungal infection requiring intravenous antibiotics at randomisation.
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of randomisation.
- Severe hepatic disease: Child-Pugh Class B or C hepatic disease.
- Known acquired immune deficiency syndrome (AIDS); the study treatment could impact blood count.
- Patients with any other disease or illness which requires hospitalization or is incompatible with the study treatment are not eligible.
- Patients unable to comply with study obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the study.
- Patients enrolled in another therapeutic study within 30 days prior of randomisation.
- Person deprived of their liberty or under protective custody or guardianship.
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
France17 sites
ICO Paul Papin
Angers, 49055
Institut Bergonie
Bordeaux, 33076
Centre Francois Baclesse
Caen, 14000
Centre Georges-Francois Leclerc
Dijon, 21079
Chu Grenoble
Grenoble, 38043
Centre Oscar Lambret
Lille, 59000
Hôpital Universitaire Dupuytren
Limoges, 87042
Groupe Hospitalier Bretagne Sud
Lorient, 56100
Centre Léon Bérard
Lyon, 69008
CHU La Timone
Marseille, 13385
Saint Louis
Paris, 75010
Hopital Europeen Georges Pompidou
Paris, 75015
Chp Saint-Gregoire
Saint-Grégoire, 35760
ICO - site René Gauducheau
Saint-Herblain, 44805
Institut de Cancérologie Lucien Neuwirth
Saint-Priest-en-Jarez, 42270
Institut Claudius Regaud
Toulouse, 31059
Clinique Pasteur
Toulouse, 31076
About this study
Official title: Adjuvant Radiotherapy in Patients With Pathological High-risk Bladder Cancer: A Randomized Multicentre Phase II Study
This is a randomized multicentre study in patients with high-risk MIBC to investigate adjuvant radiotherapy after radical cystectomy and pelvic lymph node dissection.
The objective of the study is to provide evidence that adjuvant radiotherapy improves loco-regional control with potential benefits in survival. The study will also evaluate the quality of life of patients and the tolerance of the treatment.
Read the detailed description
INDICATION:
Patients with pathological high-risk muscle invasive bladder cancer treated by radical cystectomy and pelvic lymph nodes dissection
METHODOLOGY:
Multicenter randomised phase II study in high-risk bladder cancer patients treated by radical cystectomy with pelvic lymph nodes dissection assessing :
- Experimental Arm: adjuvant pelvic radiotherapy consisting of 28 x 1.8 Gy fractions (total dose of 50.4 Gy), 5 days per week, 1 fraction /day (duration of RT is 38 days).
- Standard Arm: surveillance. Eligible patients will be randomised, in a 3:1 ratio, to receive either: adjuvant pelvic radiotherapy (Experimental Arm), or surveillance (Standard Arm).
PRIMARY OBJECTIVE:
The primary objective of the trial is to assess the efficacy of adjuvant radiotherapy in patients with high-risk bladder cancer after radical cystectomy and pelvic lymph nodes dissection. Efficacy will be assessed in terms of pelvic recurrence-free survival (PRFS) at 3 years.
SECONDARY OBJECTIVES:
For each treatment arm (adjuvant pelvic radiotherapy [Experimental Arm], or surveillance [Standard Arm]), these objectives will be evaluated independently.
- To evaluate 5-year pelvic recurrence-free survival (PRFS)
- To evaluate disease-free survival (DFS) at 3 and 5 years.
- To evaluate overall survival (OS) at 3 and 5 years.
- To evaluate metastasis-free survival (MFS) at 3 and 5 years.
- To evaluate disease-specific survival (DSS) at 3 and 5 years.
- To evaluate the tolerance and safety of each treatment strategy.
- To evaluate patients' quality of life.
Ancillary studies Objectives:
- Investigation of individual predisposition to develop radiotherapy induced late digestive toxicity using the radiation-induced lymphocyte apoptosis (RILA) assay
- The analyse of genomic and transcriptome correlation between different clusters and oncological outcomes
- Dosimetric banking to evaluate the correlation of Dose-Volume Histogram with:
- Gastrointestinal toxicity grade ≥2;
- Pelvic recurrence (radiotherapy volumes, mapping of recurrences).
- Conditions
- Patients With High-risk MIBC
- Being tested
- pelvic radiotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pelvic radiotherapyRadiation
adjuvant pelvic radiotherapy consisting of 28 x 1.8 Gy fractions (total dose of 50.4 Gy), 5 days per week, 1 fraction / day (duration of RT is 38 days).
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm | Experimental | adjuvant pelvic radiotherapy consisting of 28 x 1.8 Gy fractions (total dose of 50.4 Gy), 5 days per week, 1 fraction / day (duration of RT is 38 days). Receives: Radiation: pelvic radiotherapy |
| Standard Arm | No intervention | Surveillance |
What is being measured
The primary outcome is the main question the study is designed to answer.
pelvic recurrence-free survival (PRFS)
The PRFS is defined as the delay between randomization and pelvic recurrence or death, whichever occurs first. The pelvic recurrence will be evaluated according to RECIST V1.1 criteria.
Measured: 3 years
Secondary outcomes (13)
pelvic recurrence-free survival (PRFS)
The PRFS is defined as the delay between randomization and pelvic recurrence or death, whichever occurs first. The pelvic recurrence will be evaluated according to RECIST V1.1 criteria.
Measured: 5 years
Disease-free survival (DFS)
DFS is defined as the delay between randomization and tumor progression (local, regional, or distant) or death of any cause, whichever occurs first.
Measured: 3 years
Disease-free survival (DFS)
DFS is defined as the delay between randomization and tumor progression (local, regional, or distant) or death of any cause, whichever occurs first.
Measured: 5 years
Overall Survival (OS)
OS is defined as the delay between randomization and death, of any cause.
Measured: 3 years
Overall Survival (OS)
OS is defined as the delay between randomization and death, of any cause.
Measured: 5 years
Metastasis-free survival (MFS)
MFS is defined as the delay between randomization, and metastasis (clinical or radiological) or death of any cause whichever occurs first.
Measured: 3 years
Metastasis-free survival (MFS)
MFS is defined as the delay between randomization, and metastasis (clinical or radiological) or death of any cause whichever occurs first.
Measured: 5 years
Disease-specific survival (DSS)
DSS is defined as the delay between randomization and death due to bladder cancer.
Measured: 3 years
Disease-specific survival (DSS)
DSS is defined as the delay between randomization and death due to bladder cancer.
Measured: 5 years
Tolerance will be evaluated by toxicity: acute (<6 months after RT) and late (≥6 months after RT), assessed using the NCI CTCAE Version N°4.0
The tolerance will be evaluated by toxicity: acute (<6 months after RT) and late (≥6 months after RT), assessed using the NCI CTCAE Version N°4.0.
Measured: 5 years
Patients' quality of Life
EORTC QLQ-C30
Measured: 5 years
Patient quality of Life
The Bladder Cancer Index (BCI)
Measured: 5 years
Evaluation of acute and late toxicities
The safety will be evaluated by toxicity: acute (<6 months after RT) and late (≥6 months after RT), assessed using the NCI CTCAE Version N°4.0.
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 posted6 Nov 2017
- Study start19 Apr 2018
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Patients With High-risk MIBCStudies of the same condition, open and under way.
- More trials run by UNICANCERThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNICANCER
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paul SARGOS, MD, Principal investigator, Institut BergoniéStéphane LARRE, Prof, Principal investigator, CHU Robert DebréGéraldine PIGNOT, MD, Principal investigator, Institut Paoli-Calmettes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03333356
- Sponsor's protocol ID
- UC-0160/1617
- Other IDs
- 2016-A01535-46
- Acronym
- Bladder-ART
- Status last verified
- Dec 2024
- First submitted
- 30 Oct 2017
- Last updated
- 4 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjuvant Radiotherapy in Patients With Pathological High-risk Bladder Cancer: A Randomized Multicentre Phase II Study
- ClinicalTrials.gov ID
- NCT03333356
- Acronym / sponsor ID
- Bladder-ART / UC-0160/1617
- Conditions
- Patients With High-risk MIBC
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 81 participants (actual)
- Lead sponsor
- UNICANCERUniversity, hospital or other
- Study start
- 19 Apr 2018 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 6 Nov 2017 (actual)
- 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.
This is a randomized multicentre study in patients with high-risk MIBC to investigate adjuvant radiotherapy after radical cystectomy and pelvic lymph node dissection.
The objective of the study is to provide evidence that adjuvant radiotherapy improves loco-regional control with potential benefits in survival. The study will also evaluate the quality of life of patients and the tolerance of the treatment.
Detailed description
INDICATION:
Patients with pathological high-risk muscle invasive bladder cancer treated by radical cystectomy and pelvic lymph nodes dissection
METHODOLOGY:
Multicenter randomised phase II study in high-risk bladder cancer patients treated by radical cystectomy with pelvic lymph nodes dissection assessing :
- Experimental Arm: adjuvant pelvic radiotherapy consisting of 28 x 1.8 Gy fractions (total dose of 50.4 Gy), 5 days per week, 1 fraction /day (duration of RT is 38 days).
- Standard Arm: surveillance. Eligible patients will be randomised, in a 3:1 ratio, to receive either: adjuvant pelvic radiotherapy (Experimental Arm), or surveillance (Standard Arm).
PRIMARY OBJECTIVE:
The primary objective of the trial is to assess the efficacy of adjuvant radiotherapy in patients with high-risk bladder cancer after radical cystectomy and pelvic lymph nodes dissection. Efficacy will be assessed in terms of pelvic recurrence-free survival (PRFS) at 3 years.
SECONDARY OBJECTIVES:
For each treatment arm (adjuvant pelvic radiotherapy [Experimental Arm], or surveillance [Standard Arm]), these objectives will be evaluated independently.
- To evaluate 5-year pelvic recurrence-free survival (PRFS)
- To evaluate disease-free survival (DFS) at 3 and 5 years.
- To evaluate overall survival (OS) at 3 and 5 years.
- To evaluate metastasis-free survival (MFS) at 3 and 5 years.
- To evaluate disease-specific survival (DSS) at 3 and 5 years.
- To evaluate the tolerance and safety of each treatment strategy.
- To evaluate patients' quality of life.
Ancillary studies Objectives:
- Investigation of individual predisposition to develop radiotherapy induced late digestive toxicity using the radiation-induced lymphocyte apoptosis (RILA) assay
- The analyse of genomic and transcriptome correlation between different clusters and oncological outcomes
- Dosimetric banking to evaluate the correlation of Dose-Volume Histogram with:
- Gastrointestinal toxicity grade ≥2;
- Pelvic recurrence (radiotherapy volumes, mapping of recurrences).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental Arm | Experimental | Radiation: pelvic radiotherapyadjuvant pelvic radiotherapy consisting of 28 x 1.8 Gy fractions (total dose of 50.4 Gy), 5 days per week, 1 fraction / day (duration of RT is 38 days). |
| Standard Arm | No intervention | –Surveillance |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients with histologically-confirmed muscle-invasive bladder cancer, either with pure urothelial carcinomas, or dominant urothelial carcinomas (>50%) combined with other histological variants including: micropapillary, epidermoid, or adenocarcinomas, are eligible. Patients with small cell variants, pure adenocarcinomas, or pure epidermoid carcinomas are not eligible.
- Patients with radical cystectomy and pelvic lymph nodes dissection with no microscopic residual disease (R0 and R1).
- Note that only R1 patients without urinary diversion as orthotropic neo-bladder replacement are eligible for the study, to limit cystectomy bed radiation induced toxicities.
- Patients with tumours of TNM staging: pN0-2, M0 by imagery, and pT3a, pT3b, pT4a, and pT4b, as well as, pTX-pN1-2, pTX-NX-R1 are eligible.
- Patients having received neo-adjuvant or adjuvant chemotherapy treatment are eligible. Randomization is allowed only if AE due to chemotherapy are ≤grade 2 at randomization.
Key exclusion criteria (22 listed)
- Patient must not be enrolled if he/she fulfils any of the following non-inclusion criteria:
- Patients with R1 resection and with orthotropic neo-bladder reconstruction as urinary diversion are not eligible.
- Patients with clinical or radiological evidence of metastases or N3 staged bladder cancer are not eligible.
- Prior invasive solid tumours or haematological malignancies unless disease free for a minimum of 3 years prior to randomisation except:
- Prior pelvic radiotherapy.
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 |
|---|---|---|
| pelvic radiotherapyadjuvant pelvic radiotherapy consisting of 28 x 1.8 Gy fractions (total dose of 50.4 Gy), 5 days per week, 1 fraction / day (duration of RT is 38 days). | Radiation | Experimental Arm |
Primary outcome
pelvic recurrence-free survival (PRFS)
Time frame: 3 years
The PRFS is defined as the delay between randomization and pelvic recurrence or death, whichever occurs first. The pelvic recurrence will be evaluated according to RECIST V1.1 criteria.
13 secondary outcomes
pelvic recurrence-free survival (PRFS)
Time frame: 5 years
Disease-free survival (DFS)
Time frame: 3 years
Disease-free survival (DFS)
Time frame: 5 years
Overall Survival (OS)
Time frame: 3 years
Overall Survival (OS)
Time frame: 5 years
Metastasis-free survival (MFS)
Time frame: 3 years
Metastasis-free survival (MFS)
Time frame: 5 years
Disease-specific survival (DSS)
Time frame: 3 years
Disease-specific survival (DSS)
Time frame: 5 years
Tolerance will be evaluated by toxicity: acute (<6 months after RT) and late (≥6 months after RT), assessed using the NCI CTCAE Version N°4.0
Time frame: 5 years
Patients' quality of Life
Time frame: 5 years
Patient quality of Life
Time frame: 5 years
Evaluation of acute and late toxicities
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2024.
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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.
Paul SARGOS, MD principal investigator
Institut Bergonié
Stéphane LARRE, Prof principal investigator
CHU Robert Debré
Géraldine PIGNOT, MD principal investigator
Institut Paoli-Calmettes
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing pelvic radiotherapy in people with Patients With High-risk MIBC, run by UNICANCER at 17 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 16 inclusion and 22 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: under way, not looking for participants, as of the sponsor's last update on 4 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
pelvic recurrence-free survival (PRFS) (time frame: 3 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 4 Dec 2024.