A Phase II Trial Evaluating an Organ-conserving Strategy by Radiochemotherapy for Muscle-infiltrative Bladder Cancer (GETUG V04)
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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 |
- 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.
- 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.
|
| 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 |
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| Contact: David Azria, MD., Ph D | +33 4 67 61 31 35 | David.Azria@montpellier.unicancer.fr |
| 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 | |
More Information
No publications provided
| 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: | December 26, 2011 |
| 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 Carcinoma, Transitional Cell Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Neoplasms Urinary Bladder Diseases Urologic Diseases Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Gemcitabine Cisplatin |
Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Radiation-Sensitizing Agents Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors |
ClinicalTrials.gov processed this record on May 21, 2013