Clinical trial NCT03511391: CHEckpoint Inhibition in Combination With an Immunoboost of External Beam Radiotherapy in Solid Tumors
Official title: CHEckpoint Inhibition in Combination With an Immunoboost of External Beam Radiotherapy in Solid Tumors: CHEERS-trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Urothelial Carcinoma
Melanoma
Renal Cell Carcinoma
Non-small Cell Lung Cancer
Head and Neck Cancer
Keywords: radiotherapy
checkpoint inhibitors
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: GZA Ziekenhuizen Campus Sint-Augustinus
name: AZ Sint-Lucas Brugge
name: Jules Bordet Institute
name: AZ Sint-Lucas Gent
First posted: 2018-04-27
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival
timeFrame: 15 months
Secondary outcomes:
measure: Overall survival
timeFrame: 2 years after start trial treatment
measure: Tumor response as per RECIST
timeFrame: 12 weeks
measure: Tumor response as per iRECIST
timeFrame: 12 weeks
measure: Incidence of Treatment-Related Adverse Events [safety and tolerability]
timeFrame: 12 weeks
measure: Patient-reported quality of life
timeFrame: 12 weeks
measure: Systemic immune response
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: AZ Sint-Lucas
state: Oost-Vlaanderen
city: Brugge
country: Belgium
facility: AZ Sint-Lucas
state: West-Vlaanderen
city: Antwerp
country: Belgium
facility: GasthuisZusters Antwerpen
city: Brussels
country: Belgium
facility: Jules Bordet Institute
city: Ghent
country: Belgium
facility: University Hospital Ghent
Study officials:
affiliation: University Ghent
name: Piet Ost, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.