Consolidative Radiotherapy for Metastatic Urothelial Bladder Cancer Patients Without Progression and With no More Than Three Residual Metastatic Lesions Following First Line Systemic Therapy

Phase 2

Recruiting

• Conditions: Urothelial Bladder Cancer
• Interventions: Radiation: Experimental arm

• Registration Number: NCT04428554
• Lead Sponsor: Institut Claudius Regaud

Brief Summary

This is a Phase II, multicenter, randomized open-label and comparative study that has been designed to evaluate whether local consolidative radiotherapy in addition to standard of care improves overall survival as compared with standard of care in patients with regional and/or distant metastatic urothelial bladder cancer who have no disease progression and with no more than three residual distant metastatic lesions following the initial phase of first-line systemic therapy.

Each patient will be followed during 4 years from the date of randomization.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-06-09
• Study First Submitted QC: 2020-06-10
• Study First Posted: 2020-06-11
• Study Start: 2020-06-30
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-02
• Last Update Posted: 2024-10-04
• Primary Completion: 2028-07
• Study Completion: 2028-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

1. Age ≥ 18 years

2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

3. Urothelial bladder cancer histologically proven (both pure urothelial cancers and mixed histologic features are allowed)

4. Metastatic patients to regional nodes (Tx,N1-N3,M0) and/or distant sites (Tx,Nx,M1a-M1b) documented with contrast-enhanced CT-scanner of the chest, abdomen and pelvis, either de novo or presenting first regional/distant relapse following cystectomy (with no local recurrence in the cystectomy bed)

5. Completion of the initial phase (4-6 cycles) of 1st line metastatic treatment (systemic therapy by chemotherapy and/or immunotherapy by immune check-point inhibitor according to standard recommendations). Patients having started maintenance therapy are eligible.

6. No disease progression after the initial phase of first-line metastatic systemic therapy according to RECIST v1.1

7. No more than 3 residual distant metastatic lesions following the initial phase of first-line metastatic systemic therapy:

   1. Regional nodes (below aortic bifurcation) are not included in the count of distant metastatic lesions

   2. The number of distant residual lesions is determined on the basis of the imaging modality for tumor response assessment performed after systemic treatment according to local habits (CT-scan or 18FDG PET-CT if performed):

      In case of response assessment by CT-scanner only: residual lesions are all remaining visible lesions In case of response assessment by additional 18FDG PET-CT: residual lesions are only the lesions with residual hyperfixation

   3. Regarding distant lymph nodes metastases:

      • If evaluation is performed by CT-scanner only, residual lymph nodes are considered pathological according to one or several criteria among: Short axis ≥ 1cm/Central necrosis/Heterogeneous contrast enhancement
      • Residual para-aortic nodes involvement accounts for one lesion, even if several para-aortic nodes are involved.
      • Other nodes: each involved node accounts for one lesion.

8. Residual distant metastases (if applicable) eligible for SBRT in terms of dose constraints to the organs at risk, with no prior radiotherapy interfering with SBRT

9. 8 weeks or less between last cycle of the initial phase of systemic treatment and randomization

10. No contraindication to pelvic radiotherapy

11. Signed informed consent

12. Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol

13. Patient affiliated to a Social Health Insurance in France

Exclusion Criteria

1. Non-transitional cell histology (Squamous cell carcinoma, adenocarcinoma or neuroendocrine carcinoma of the bladder)
2. Brain metastases before systemic treatment
3. Liver metastases before systemic treatment
4. Absence of target to be irradiated (i.e. previous cystectomy + no residual distant lesions following systemic treatment + no pelvic or para-aortic nodes at metastatic presentation)
5. Patient with relapse following definitive chemoradiation of the bladder
6. Local recurrence in the cystectomy bed following cystectomy
7. Previous pelvic irradiation
8. Prior radiotherapy near the residual metastatic lesions precluding ablative SBRT
9. Active inflammatory bowel disease
10. Contraindication to SBRT of a lesion due to organ dysfunction; in particular, patients with lung lesions and documented or suspected interstitial lung disease should not be included
11. History of scleroderma
12. Current or past history of second neoplasm diagnosed within the last 5 years (except basocellular carcinoma and prostate cancer incidentally discovered during previous cystoprostatetectomy and pelvic lymph node dissection and with a good prognosis [T stage <pT3b and Gleason <8 and pN- and post-operative PSA <0.1 ng/mL])
13. Pregnancy or breast feeding or inadequate contraceptive measures
14. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
15. Any psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the provision of informed consent or compliance to study procedure
16. Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice).
17. Concurrent enrolment in another interventional therapeutic clinical study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental arm	Experimental arm	-

Primary Outcome Measures

Name	Time	Method
Overall Survival	4 years for each patient

Secondary Outcome Measures

Name	Time	Method
Safety will be assessed by the toxicity grading of the National Cancer Institute (NCI-CTCAE v5)	4 years for each patient
Quality of life will be evaluated by the EORTC QLQ-C-30 questionnaire	4 years for each patient
Progression Free Survival	4 years for each patient

Trial Locations

Locations (18)

Institut Andrée Dutreix; 🇫🇷 Dunkerque, France

Clinique Claude Bernard; 🇫🇷 Albi, France

CHU Besançon; 🇫🇷 Besançon, France

Centre Francois Baclesse; 🇫🇷 Caen, France

Institut Curie; 🇫🇷 Paris, France

Centre Oscar Lambret; 🇫🇷 Lille, France

Institut Paoli-Calmettes; 🇫🇷 Marseille, France

Centre Antoine Lacassagne; 🇫🇷 Nice, France

Institut Bergonie; 🇫🇷 Bordeaux, France

Clinique Pasteur-Lanroze; 🇫🇷 Brest, France

Institut de Cancerologie de L'Ouest; 🇫🇷 Saint-Herblain, France

Chu Morvan; 🇫🇷 Brest, France

Centre Jean Perrin; 🇫🇷 Clermont-Ferrand, France

Groupement de Radiothérapie et d'Oncologie des Pyrénées; 🇫🇷 Pau, France

HIA Bégin; 🇫🇷 Saint-Mandé, France

Institut de Cancerologie Lucien Neuwirth; 🇫🇷 Saint-Priest-en-Jarez, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France

Institut Universitaire du Cancer Toulouse Oncopole; 🇫🇷 Toulouse, France