Checkpoint inhibition in combination with an immunoboost of external beam radiotherapy in solid tumors (CHEERS): study protocol for a phase 2, open-label, randomized controlled trial

BMC Cancer

Vibeke Kruse¹  Piet Ost²  Pieter Mestdagh³  Dries Reynders⁴  Els Goetghebeur⁴  Annabel Meireson⁵  Lieve Brochez⁵  Eva Hulstaert⁶  Vincent Renard⁷  Sylvie Rottey⁸  Daan De Maeseneer⁹  Veerle Surmont^1,10  Nora Sundahl^1,11  Mathieu Spaas^1,11  Piet Dirix^1,12  Robbe Van den Begin^1,13  Dirk Van Gestel^1,13 

[1] Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium;Medical Oncology, Ghent University Hospital, Ghent, Belgium;Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium;Radiation Oncology, Iridium Cancer Network, Wilrijk, Belgium;Center for Medical Genetics (CMGG), Ghent University, Ghent, Belgium;Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium;Department of Applied Mathematics, Computer Science and Statistics & Stat-Gent CRESCENDO Consortium, Ghent University, Ghent, Belgium;Dermatology, Ghent University Hospital, Ghent, Belgium;Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium;Dermatology, Ghent University Hospital, Ghent, Belgium;Center for Medical Genetics (CMGG), Ghent University, Ghent, Belgium;Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium;Medical Oncology, AZ Sint-Lucas, Ghent, Belgium;Medical Oncology, Ghent University Hospital, Ghent, Belgium;Medical Oncology, Ghent University Hospital, Ghent, Belgium;Medical Oncology, AZ Sint-Lucas, Bruges, Belgium;Pulmonary Medicine, Ghent University Hospital, Ghent, Belgium;Radiation Oncology, Ghent University Hospital, C. Heymanslaan 10, B-9000, Ghent, Belgium;Radiation Oncology, Iridium Cancer Network, Wilrijk, Belgium;Radiation Oncology, Jules Bordet Insitute, Université Libre de Bruxelles, Brussels, Belgium;

关键词: Head and neck squamous cell carcinoma;    Melanoma;    Non-small-cell lung carcinoma;    Renal cell carcinoma;    Transitional cell carcinoma;    Immunotherapy;    Checkpoint inhibitor;    Stereotactic body radiotherapy;    Survival;    Clinical trial;   

DOI  :  10.1186/s12885-021-08088-w

来源: Springer

【 摘 要 】

BackgroundWhile the introduction of checkpoint inhibitors (CPIs) as standard of care treatment for various tumor types has led to considerable improvements in clinical outcome, the majority of patients still fail to respond. Preclinical data suggest that stereotactic body radiotherapy (SBRT) could work synergistically with CPIs by acting as an in situ cancer vaccine, thus potentially increasing response rates and prolonging disease control. Though SBRT administered concurrently with CPIs has been shown to be safe, evidence of its efficacy from large randomized trials is still lacking. The aim of this multicenter randomized phase II trial is to assess whether SBRT administered concurrently with CPIs could prolong progression-free survival as compared to standard of care in patients with advanced solid tumors.Methods/designNinety-eight patients with locally advanced or metastatic disease will be randomized in a 1:1 fashion to receive CPI treatment combined with SBRT (Arm A) or CPI monotherapy (Arm B). Randomization will be stratified according to tumor histology (melanoma, renal, urothelial, head and neck squamous cell or non-small cell lung carcinoma) and disease burden (≤ or > 3 cancer lesions). The recommended SBRT dose is 24Gy in 3 fractions, which will be administered to a maximum of 3 lesions and is to be completed prior to the second or third CPI cycle (depending on CPI treatment schedule). The study’s primary endpoint is progression-free survival as per iRECIST. Secondary endpoints include overall survival, objective response, local control, quality of life and toxicity. Translational analyses will be performed using blood, fecal and tissue samples. Discussion: The CHEERS trial will provide further insights into the clinical and immunological impact of SBRT when combined with CPIs in patients with advanced solid tumors. Furthermore, study results will inform the design of future immuno-radiotherapy trials. Trial registrationClinicaltrials.gov identifier: NCT03511391. Registered 17 April 2018.

【 授权许可】

CC BY