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01-12-2021 | Kidney Cancer | Study protocol

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

Authors: Mathieu Spaas, Nora Sundahl, Eva Hulstaert, Vibeke Kruse, Sylvie Rottey, Daan De Maeseneer, Veerle Surmont, Annabel Meireson, Lieve Brochez, Dries Reynders, Els Goetghebeur, Robbe Van den Begin, Dirk Van Gestel, Vincent Renard, Piet Dirix, Pieter Mestdagh, Piet Ost

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

While 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/design

Ninety-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 registration

Clinicaltrials.gov identifier: NCT03511391. Registered 17 April 2018.

Available only for authorised users

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Title: 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
Authors: Mathieu Spaas
Nora Sundahl
Eva Hulstaert
Vibeke Kruse
Sylvie Rottey
Daan De Maeseneer
Veerle Surmont
Annabel Meireson
Lieve Brochez
Dries Reynders
Els Goetghebeur
Robbe Van den Begin
Dirk Van Gestel
Vincent Renard
Piet Dirix
Pieter Mestdagh
Piet Ost
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Kidney Cancer
Solid Tumor
Melanoma
Melanoma
Kidney Cancer
Kidney Cancer
Radiotherapy
Checkpoint Inhibitors
Urothelial Cancer
Urothelial Cancer
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08088-w

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Abstract

Background

Methods/design

Trial registration

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