CHEckpoint Inhibition in Combination With an Immunoboost of External Beam Radiotherapy in Solid Tumors (CHEERS)

CHEckpoint Inhibition in Combination With an Immunoboost of External Beam Radiotherapy in Solid Tumors: CHEERS-trial

This randomized controlled phase II trial will investigate whether the addition of stereotactic body radiotherapy to checkpoint inhibitor treatment in patients with non-small-cell lung carcinoma, urothelial carcinoma, renal cell carcinoma, melanoma or head-and-neck carcinoma can improve progression-free survival as compared to checkpoint inhibitor monotherapy. The primary outcome is progression-free survival; secondary outcomes include overall survival, response according to iRecist and Recist v1.1 and toxicity.

Study Overview

• Status: Completed
• Conditions: Melanoma; Renal Cell Carcinoma; Head and Neck Cancer; Non-small Cell Lung Cancer; Urothelial Carcinoma
• Intervention / Treatment: Drug: Nivolumab or Pembrolizumab or Atezolizumab; Radiation: SBRT

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, 2000
    • GasthuisZusters Antwerpen
  • Brussels, Belgium, 1000
    • Jules Bordet Institute
  • Ghent, Belgium, 9000
    • University Hospital Ghent
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • AZ Sint-Lucas
  • West-Vlaanderen
    • Brugge, West-Vlaanderen, Belgium, 8000
      • AZ Sint-Lucas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Before patient registration, written informed consent must be given according to ICH/GCP and national/local regulations.
• Histologically confirmed diagnosis of a solid tumour.
• At least one extracranial tumour lesion available for radiotherapy administration.
• Patient will receive a checkpoint inhibitor per standard of care in one of the following settings (locally advanced or metastatic): melanoma (1st - 3rd line nivolumab or pembrolizumab); renal cell carcinoma (2nd line nivolumab); non-small cell lung carcinoma (2nd or 3rd line nivolumab, pembrolizumab or atezolizumab); urothelial cell carcinoma ( 1st-3rd line nivolumab, pembrolizumab or atezolizumab); head-& neck squamous cell carcinoma (1st-2nd line pembrolizumab, 2nd line nivolumab).
• Karnofsky Performance status > 60.
• Age 18 years or older.

Exclusion Criteria:

• Prior radiotherapy preventing treatment with SBRT.
• Prior treatment with an anti-PD-(L)1 antibody.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or prostate cancer that has undergone potentially curative therapy and with normalized PSA.
• Uncontrolled central nervous system (CNS) metastases at baseline (controlled = previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants), and/or carcinomatous meningitis.
• Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medication within 14 days prior to the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
• Has a diagnosis of immunodeficiency or history of human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection.
• Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study.
• Patient not likely to comply with the protocol; I.e. uncooperative attitude, inability to return for follow-up visits and unlikely to complete the study.
• Contraindication for radiotherapy.
• Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental arm; Stereotactic body radiotherapy concurrent with checkpoint inhibitor treatment: Nivolumab or Pembrolizumab or Atezolizumab + SBRT	Drug: Nivolumab or Pembrolizumab or Atezolizumab; per national standard of care; Other Names: Immune checkpoint inhibitor; Radiation: SBRT; Stereotactic body radiotherapy is administered to maximally 3 lesions in 3 fractions of 8Gy prior to the second/third cycle of checkpoint inhibitors.; Other Names: Stereotactic body radiotherapy, SABR, Stereotactic ablative radiotherapy
Active Comparator: Control arm; Checkpoint inhibitor treatment only: Nivolumab or Pembrolizumab or Atezolizumab monotherapy	Drug: Nivolumab or Pembrolizumab or Atezolizumab; per national standard of care; Other Names: Immune checkpoint inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Progression-free survival will be defined as the time from randomization to disease progression (as per iRECIST) or death from any cause.	15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival will be defined as the time from randomization to death from any cause.	2 years after start trial treatment
Tumor response as per RECIST	Response of non-irradiated lesions will be evaluated as per RECIST v1.1.	12 weeks
Tumor response as per iRECIST	Response of non-irradiated lesions will be evaluated as per iRECIST	12 weeks
Incidence of Treatment-Related Adverse Events [safety and tolerability]	Adverse events will be monitored as per Common Terminology Criteria for Adverse Events (CTCAE) v5.0	12 weeks
Patient-reported quality of life	Quality of life will be assessed as per EORTC-QLQ C30 questionnaire	12 weeks
Systemic immune response	Exploratory translational analyses will be performed using blood and fecal samples	12 weeks

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: Jules Bordet Institute; AZ Sint-Lucas Gent; GZA Ziekenhuizen Campus Sint-Augustinus; AZ Sint-Lucas Brugge
• Investigators: Principal Investigator: Piet Ost, PhD, University Ghent

Publications and helpful links

General Publications

• Spaas M, Sundahl N, Hulstaert E, Kruse V, Rottey S, De Maeseneer D, Surmont V, Meireson A, Brochez L, Reynders D, Goetghebeur E, Van den Begin R, Van Gestel D, Renard V, Dirix P, Mestdagh P, Ost P. 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. 2021 May 7;21(1):514. doi: 10.1186/s12885-021-08088-w.
• Spaas M, Sundahl N, Kruse V, Rottey S, De Maeseneer D, Duprez F, Lievens Y, Surmont V, Brochez L, Reynders D, Danckaert W, Goetghebeur E, Van den Begin R, Van Gestel D, Renard V, Dirix P, Ost P. Checkpoint Inhibitors in Combination With Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors: The CHEERS Phase 2 Randomized Clinical Trial. JAMA Oncol. 2023 Sep 1;9(9):1205-1213. doi: 10.1001/jamaoncol.2023.2132.

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2018
• Primary Completion (Actual): February 1, 2022
• Study Completion (Actual): January 23, 2024

Study Registration Dates

• First Submitted: April 17, 2018
• First Submitted That Met QC Criteria: April 17, 2018
• First Posted (Actual): April 27, 2018

Study Record Updates

• Last Update Posted (Estimated): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: radiotherapy; checkpoint inhibitors
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Nivolumab; Pembrolizumab; Immune Checkpoint Inhibitors; Atezolizumab
• Other Study ID Numbers: EC2017/1678

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No