A Phase II Trial Evaluating an Organ-conserving Strategy by Radiochemotherapy for Muscle-infiltrative Bladder Cancer (GETUGV04)

December 5, 2023 updated by: Institut du Cancer de Montpellier - Val d'Aurelle

A Randomized Phase II Trial Evaluating an Organ-conserving Strategy With Radiotherapy + CDDP + Gemcitabine vs Radiotherapy + CDDP in Muscle-infiltrative Bladder Cancer

If radical cystectomy remains the standard of care for muscle invasive bladder cancer, consequences of this surgical procedure are often harsh. Over the past years, concurrent chemo-radiotherapy has imposed itself as an alternative treatment. Published data on concomitant radiochemotherapy (radiotherapy/cisplatin or radiotherapy/cisplatin/5-fluorouracil combinations) showed local control rates with bladder preservation at 5 years ranging from 40% to 65% according to the disease stage, and overall survival probabilities ranging from 40% to 50% at 5 years. In order to improve local and systemic prognosis, evaluation of other chemotherapy agents with higher radiosensitizing effect, such as gemcitabine, is justified. Gemcitabine possesses its own anti-cancer activities on urothelial diseases and has a synergetic activity with cisplatin. The investigators completed a monocenter phase I study combining radiotherapy, cisplatin, and twice-weekly gemcitabine, and determined a recommended dose of gemcitabine 25 mg/m². The objective of the present study is to evaluate the combination of radiotherapy + cisplatin + gemcitabine in terms of disease-free survival in non metastatic muscle invasive urothelial cancer patients.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The objective of the present study is to evaluate the combination of radiotherapy + cisplatin + gemcitabine in terms of disease-free survival in non metastatic muscle invasive urothelial cancer patients.

Study Type

Interventional

Enrollment (Actual)

69

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Bordeaux, France, 33000
        • Institut Bergonie
      • Caen, France, 14000
        • Centre Francois Baclesse
      • Créteil, France, 94010
        • Hôpital Henri Mondor
      • Dijon, France, 21000
        • CRLC GF Leclerc
      • Montpellier, France, 34000
        • CRLC Val d'Aurelle-Paul Lamarque
      • Mougins, France, 06250
        • Centre Azuréen de Cancérologie
      • Nice, France, 06189
        • Centre Antoine Lacassagne
      • Paris, France, 75010
        • Hôpital Saint louis
      • Paris, France, 75015
        • HEGP
      • Saint-Priest-en-Jarez, France, 42705
        • Institut de Cancérologie Lucien Neuwirth
      • Toulouse, France, 31300
        • Clinique Patseur
      • Vandœuvre-lès-Nancy, France, 54511
        • Centre Alexis Vautrin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Muscle invasive urothelial cancer (front line or following the progression of a superficial tumor), pT2-pT3 stage without lymphatic impairment (N0) and without detectable metastases (M0). An optimal macroscopic resection (TURB) have to be performed
  • The proof of invasive tumor to the muscle should be brought by a transurethral resection under anaesthesia less than 8 weeks before or, in the absence, by superficial biopsies and formal imaging. Multiples biopsies in the bladder must also be performed.
  • Age ≥ 18 years
  • Life expectancy ≥ 6 months
  • Kanorfsky index ≥ 70 % (WHO 0, 1, 2)
  • Biological criteria: neutrophils ≥ 1500/mm3, Platelets ≥ 100 000/mm3, haemoglobin ≥ 10 g/dl, creatinine clearance > 60 ml/mn
  • No distant metastases (Thorax, abdomen, and pelvic CT-scan, bone scan)
  • Efficient contraception for premenopausal women, maintained during the whole treatment and up to two months after the completion of radiotherapy.
  • No radiotherapy or chemotherapy history except for in situ bladder lesions.
  • No carcinological history except for non melanoma skin tumours, in situ uterine cervix cancer
  • No contraindication to gemcitabine or cisplatin.
  • No contraindication to radiotherapy
  • Information letter and informed consent signed
  • Patient covered by social security

Exclusion Criteria:

  • Bladder tumors without any muscle infiltration
  • Epidermoid carcinoma or adenocarcinoma
  • Distance metastases or extrapelvic node positivity
  • Severe digestive history (ulcerative colitis, complicated diverticulitis)
  • Pregnancy and breast feeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Radiotherapy + cisplatin
Other: Radiation + cisplatin

RT will encompass bilateral internal and external iliac lymph nodes at a dose of 45 Gy and the bladder up to 63 Gy. Fractionation will be 1.8 Gy per fraction.

Cisplatin: 20 mg/m2/day through continuous iv perfusion for 4 consecutive days, from D2 to D5 and from D23 to D26 for the first part of the treatment, then from D2 to D5 if an additional treatment is decided.

A cystoscopy with a transurethral resection will be performed 3 weeks after the last day of the first part of radio-chemotherapy.

  • In the absence of tumor cells, the 2nd part will start on the 4th week or at latest on the 5th week after the last day of the 1st part of radio-chemotherapy.
  • In case of a microscopic tumor residue or of a local tumor progression, operability will be re-evaluated in view of a radical cystectomy and the patient will exit the study.
Experimental: Radiotherapy + cisplatin + gemcitabine
Other: Radiation + cisplatin + gemcitabine

Radiotherapy will encompass bilateral internal and external iliac lymph nodes at a dose of 45 Gy and the bladder up to 63 Gy. Fractionation will be 1.8 Gy per fraction.

Cisplatin: 20 mg/m2/day through continuous iv perfusion for 4 consecutive days, from D2 to D5 and from D23 to D26 for the first part of the treatment, then from D2 to D5 for the second part of the treatment if an additional treatment is decided.

Gemcitabine: iv injection for 30 minutes, twice a week at a dose of 25 mg/m2 on days 2, 5, 9, 12, 16, 19, 23, 26, 30, and 33 for the 1st part of treatment, then on days 2, 5, 9, and 12 for the 2nd part of treatment if an additional treatment is decided (cystoscopy with a transurethral resection). RT will be delivered between 2 and 6 hours after completion of the gemcitabine injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free survival
Time Frame: Two years after the end of the complete therapeutic sequence
The time to relapse is defined as the time from the date of randomisation to the date of the first event. Time to relapse for patients without any event (local, regional, distance, or death) will be censored at the date of latest information.
Two years after the end of the complete therapeutic sequence

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Up to 5 years
The time to death is defined as time from the randomization to the date of death from any cause, or to the date on which latest information is obtained.
Up to 5 years
Acute and late toxicities
Time Frame: Up to 5 years
Acute and late toxicities will be scored according to the NCI-CTC v4.0.
Up to 5 years
measurement of Quality of life
Time Frame: Up to 5 years
Questionnaires QLQ C30 + QLQ-BLM30 + QLQ-ELD15 + Oncodage
Up to 5 years
Correlation between lymphocyte apoptosis and severity of late toxicities.
Time Frame: Up to 5 years
Before starting radiotherapy, 5ml of blood will be sampled in a 5ml heparinised tube to prospectively measure the rate of CD8 radio-induced lymphocyte apoptosis before any radiotherapy treatment. A correlation between the low rate of lymphocyte apoptosis and the severity of late toxicities will be studied to confirm the predictive power of this biological test on radio-induced side-effects.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut du Cancer de Montpellier - Val d'Aurelle

Investigators

  • Study Chair: Azria David, MD, ICM Val D'Aurelle

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 6, 2011

Primary Completion (Actual)

July 25, 2022

Study Completion (Estimated)

September 1, 2025

Study Registration Dates

First Submitted

December 14, 2011

First Submitted That Met QC Criteria

December 16, 2011

First Posted (Estimated)

December 20, 2011

Study Record Updates

Last Update Posted (Actual)

December 6, 2023

Last Update Submitted That Met QC Criteria

December 5, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GETUG V04
  • 2011-000408-17 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Infiltrating Bladder Urothelial Carcinoma

Clinical Trials on Radiation + cisplatin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cyprus

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe