Adjuvant Radiotherapy in Patients With Pathological High-risk Bladder Cancer (GETUG-AFU 30)

NCT ID: NCT03333356

Last Updated: 2024-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

81 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-19

Study Completion Date

2027-12-31

Brief Summary

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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

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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

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Patients With High-risk MIBC

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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).

Group Type EXPERIMENTAL

pelvic radiotherapy

Intervention Type RADIATION

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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pelvic radiotherapy

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).

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

1. 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.
2. 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.
3. 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.
4. 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.
5. Patients ≥18 years old.
6. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
7. Absolute neutrophil count (ANC) ≥1500 cells/mm³.
8. Platelets ≥100000 cells/mm³.
9. Haemoglobin ≥8 g/dL (Note: following a blood transfusion or another intervention if required).
10. 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.
11. Adequate renal function: clearance \>30 mL/min (MDRD).
12. Patients having provided written informed consent prior to any study-related procedures.
13. Patients affiliated to the social security scheme.
14. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.


1. Patients with R1 resection and with orthotropic neo-bladder reconstruction as urinary diversion are not eligible.
2. Patients with clinical or radiological evidence of metastases or N3 staged bladder cancer are not eligible.
3. 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,
* 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),
4. Prior pelvic radiotherapy.
5. Patients with active inflammatory bowel disease.
6. Patients who required surgical treatment for bowel obstruction before bladder cancer diagnosis or after cystectomy.
7. Prior chemotherapy for other malignant diseases within the previous 5 years, except for neoadjuvant pre-cystectomy chemotherapy or adjuvant chemotherapy which are permitted.
8. 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.
9. Patients with any other disease or illness which requires hospitalization or is incompatible with the study treatment are not eligible.
10. 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.
11. Patients enrolled in another therapeutic study within 30 days prior of randomisation.
12. Person deprived of their liberty or under protective custody or guardianship.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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UNICANCER

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paul SARGOS, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Bergonié

Stéphane LARRE, Prof

Role: PRINCIPAL_INVESTIGATOR

CHU Robert Debré

Géraldine PIGNOT, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Paoli-Calmettes

Locations

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ICO Paul Papin

Angers, , France

Site Status

Institut Bergonie

Bordeaux, , France

Site Status

Centre Francois Baclesse

Caen, , France

Site Status

Centre Georges-Francois Leclerc

Dijon, , France

Site Status

Chu Grenoble

Grenoble, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Hôpital Universitaire Dupuytren

Limoges, , France

Site Status

Groupe Hospitalier Bretagne Sud

Lorient, , France

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

CHU La Timone

Marseille, , France

Site Status

Saint Louis

Paris, , France

Site Status

Hopital Europeen Georges Pompidou

Paris, , France

Site Status

Chp Saint-Gregoire

Saint-Grégoire, , France

Site Status

ICO - site René Gauducheau

Saint-Herblain, , France

Site Status

Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, , France

Site Status

Institut Claudius Regaud

Toulouse, , France

Site Status

Clinique Pasteur

Toulouse, , France

Site Status

Countries

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France

Other Identifiers

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2016-A01535-46

Identifier Type: REGISTRY

Identifier Source: secondary_id

UC-0160/1617

Identifier Type: -

Identifier Source: org_study_id