Consolidative radiotherapy for metastatic urothelial bladder cancer patients without progression and with no more than three residual metastatic lesions following first line systemic therapy: A prospective randomized comparative phase II trial (BLAD RAD01/GETUG-AFU V07).

Authors

null

Jonathan Khalifa

Institut Claudius Regaud/IUCT-Oncopole, Toulouse, France

Jonathan Khalifa , Damien Pouessel , Mathieu Roumiguie , Paul Sargos , Genevieve Loos , Ulrike Schick , Naji Salem , Nathalie Mesgouez-Nebout , Yohann Loriot , Christophe Hennequin , Emmanuel Meyer , Pierre Blanchard , Valentine Guimas , Laurent Votron , Pierre Graff-Cailleaud , Gilles Crehange , Muriel Mounier , Angélique Massoubre , Leonor Chaltiel , Thomas Filleron

Organizations

Institut Claudius Regaud/IUCT-Oncopole, Toulouse, France, Institut Claudius Regaud/IUCT-Oncopole, CHU Rangueil, Toulouse, France, Institut Bergonié, Bordeaux, France, Centre Jean Perrin, Clermont-Ferrand, France, Institut de Cancérologie et d'Hématologie CHRU de Brest, Brest, France, Department of Radiotherapy, Institut Paoli-Calmettes, Marseille, France, Institut de Cancérologie de l'Ouest-site Paul Papin, Angers, France, Department of Cancer Medicine, Gustave Roussy, Université Paris-Saclay, Villejuif, France, Hopital Saint-Louis, Paris, France, Department of Radiation Oncology, Centre François Baclesse, Caen, France, Gustave Roussy, Villejuif, France, Institut de Cancérologie de l'Ouest, Nantes Saint-Herblain, France, Clinique Claude Bernard, Albi, France, Institut Curie, Paris, France

Research Funding

Other Government Agency
PHRC-K 2019 (programme hospitalier de recherche clinique national en cancérologie)

Background: Consolidative local treatment of the primary tumor in the treatment of metastatic malignancies has shown promising results in several types of tumors, mostly relying on the seed-and-soil theory. Furthermore, the local treatment of the residual metastases following systemic treatment is a promising approach, in part due to the high incidence of progression at prior sites of disease in patients who had initially responded to chemotherapy. To date, no prospective data exists on such consolidative approach in metastatic urothelial bladder cancer (mUBC). The phase II trial BLAD-RAD01 GETUG-AFU V07 was designed to investigate the role of local consolidative radiotherapy in patients with limited mUBC and without progression following the initial phase of first-line systemic therapy. Methods: This is a phase II, multicenter, randomized open-label and comparative study. Patients with mUBC (excluding brain and liver metastases), without progression following standard first-line systemic therapy according to RECIST v1.1, and with no more than 3 residual metastatic lesions on 18FDG-PET scanner and/or contrast-enhanced CT-scanner are eligible for the study. After the completion of systemic treatment, an estimated 130 patients will be randomized in a 1:1 ratio between consolidative local treatment (pelvic radiotherapy +/- previous transurethal resection of bladder tumor, associated with stereotactic body radiotherapy (SBRT) to the residual metastases) plus standard of care (arm B) and standard of care only (arm A). Stratification is performed based upon: the center, the ECOG performance status, the administration of immunotherapy or not, the number of residual metastatic lesions and the imaging modality for assessment of the number of residual lesions. To date, standard of care for this population is maintenance treatment with avelumab. Radiotherapy regimens consist in conventionally fractionated (64Gy in 32 fractions) or hypofractionated (55Gy in 20 fractions) irradiation of the bladder, optional pelvic nodes irradiation, and 3 to 5 fractions of 6 to 18 Gy in SBRT for metastases, depending on the location. The main objective is to detect an increase in 20-month overall survival rate following chemotherapy from 50% (based upon the JAVELIN 100 trial) to 66%; this corresponds to a hazard ratio of 0.6. A total of 83 events are necessary for 85% power to detect this difference if it is true using a one-sided logrank test at the 10% of significance. Target difference, type I and II error rates are relaxed and compatibles with recommendations for comparative phase II trials. Key secondary endpoints are progression free survival, safety and quality of life. To date, one patient has been enrolled and eight centers are open for accrual. Clinical trial information: NCT04428554

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Abstract Details

Meeting

2021 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Genitourinary Cancer—Kidney and Bladder

Track

Genitourinary Cancer—Kidney and Bladder

Sub Track

Bladder Cancer

Clinical Trial Registration Number

NCT04428554

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr TPS4588)

DOI

10.1200/JCO.2021.39.15_suppl.TPS4588

Abstract #

TPS4588

Poster Bd #

Online Only

Abstract Disclosures