A Phase II Trial Evaluating an Organ-conserving Strategy by Radiochemotherapy for Muscle-infiltrative Bladder Cancer (GETUG V04)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Centre Val d'Aurelle - Paul Lamarque
Sponsor:
Information provided by (Responsible Party):
Centre Val d'Aurelle - Paul Lamarque
ClinicalTrials.gov Identifier:
NCT01495676
First received: December 14, 2011
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Infiltrating Bladder Urothelial Carcinoma
Other: Radiation + cisplatin
Other: Radiation + cisplatin + gemcitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial Evaluating an Organ-conserving Strategy With Radiotherapy + CDDP + Gemcitabine vs Radiotherapy + CDDP in Muscle-infiltrative Bladder Cancer

Resource links provided by NLM:


Further study details as provided by Centre Val d'Aurelle - Paul Lamarque:

Primary Outcome Measures:
  • Disease-free survival [ Time Frame: Two years after the end of the complete therapeutic sequence ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
    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.

  • Acute and late toxicities [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Acute and late toxicities will be scored according to the NCI-CTC v4.0.

  • Quality of life [ Designated as safety issue: No ]
    Questionnaires QLQ C30 + QLQ-BLM30 + QLQ-ELD15 + Oncodage

  • Correlation between lymphocyte apoptosis and severity of late toxicities. [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 108
Study Start Date: September 2011
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01495676

Contacts
Contact: David Azria, MD., Ph D +33 4 67 61 31 35 David.Azria@montpellier.unicancer.fr

Locations
France
CRLC Val d'Aurelle-Paul Lamarque Recruiting
Montpellier, France, 34000
Contact: Jean-Pierre Bleuse, MD    +33 4 67 61 23 44    Jean-Pierre.Bleuse@montpellier.unicancer.fr   
Principal Investigator: David Azria, MD, Ph D         
Sponsors and Collaborators
Centre Val d'Aurelle - Paul Lamarque
  More Information

No publications provided by Centre Val d'Aurelle - Paul Lamarque

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Centre Val d'Aurelle - Paul Lamarque
ClinicalTrials.gov Identifier: NCT01495676     History of Changes
Other Study ID Numbers: GETUG V04, 2011-000408-17
Study First Received: December 14, 2011
Last Updated: May 7, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Val d'Aurelle - Paul Lamarque:
Bladder cancer
Organ-conserving strategy
Radiochemotherapy
non metastatic

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Gemcitabine
Cisplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 18, 2014