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

• Published in: BMC cancer Vol. 21; no. 1; pp. 514 - 10
• Main Authors: Spaas, Mathieu, Sundahl, Nora, Hulstaert, Eva, Kruse, Vibeke, Rottey, Sylvie, De Maeseneer, Daan, Surmont, Veerle, Meireson, Annabel, Brochez, Lieve, Reynders, Dries, Goetghebeur, Els, Van den Begin, Robbe, Van Gestel, Dirk, Renard, Vincent, Dirix, Piet, Mestdagh, Pieter, Ost, Piet
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 07-05-2021; BioMed Central; BMC
• Subjects: Apoptosis; Cancer vaccines; Care and treatment; Clinical trials; Clinical Trials, Phase II as Topic; Combined Modality Therapy; Disease control; Head & neck cancer; Head and neck squamous cell carcinoma; Hepatitis; Humans; Immune checkpoint; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Kidney cancer; Localization; Lung cancer; Lung carcinoma; Lung diseases; Melanoma; Metastases; Metastasis; Monoclonal antibodies; Neoplasms - mortality; Neoplasms - therapy; Non-small cell lung carcinoma; Patients; Quality of life; Radiation therapy; Radiosurgery - methods; Radiotherapy; Randomized Controlled Trials as Topic; Renal cell carcinoma; Small cell lung carcinoma; Solid tumors; Squamous cell carcinoma; Study Protocol; Testing; Toxicity; Transitional cell carcinoma; Tumors; Belgium; Checkpoint inhibitor; Stereotactic body radiotherapy; Renal cell carcinoma; Immunotherapy; Melanoma; Clinical trial; Head and neck squamous cell carcinoma; Transitional cell carcinoma; Survival; Non-small-cell lung carcinoma
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-021-08088-w

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