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

Non-small Cell Lung Cancer Clinical Trial

— CHEERS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03511391
• Other study ID #: EC2017/1678
• Status: Completed
• Phase: Phase 2
• Start date: March 9, 2018
• Est. completion date: January 23, 2024

Study information

• Verified date: January 2024
• Source: University Hospital, Ghent
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 99
• Est. completion date: January 23, 2024
• Est. primary completion date: February 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Head and Neck Cancer
• Melanoma
• Non-small Cell Lung Cancer
• Renal Cell Carcinoma
• Urothelial Carcinoma

Intervention

Drug:
• Nivolumab or Pembrolizumab or Atezolizumab
per national standard of care

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.

Locations

Country	Name	City	State
Belgium	GasthuisZusters Antwerpen	Antwerp
Belgium	AZ Sint-Lucas	Brugge	West-Vlaanderen
Belgium	Jules Bordet Institute	Brussels
Belgium	AZ Sint-Lucas	Ghent	Oost-Vlaanderen
Belgium	University Hospital Ghent	Ghent

Sponsors (5)

Lead Sponsor	Collaborator
University Hospital, Ghent	AZ Sint-Lucas Brugge, AZ Sint-Lucas Gent, GZA Ziekenhuizen Campus Sint-Augustinus, Jules Bordet Institute

Country where clinical trial is conducted

Belgium, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall survival	Overall survival will be defined as the time from randomization to death from any cause.	2 years after start trial treatment
Secondary	Tumor response as per RECIST	Response of non-irradiated lesions will be evaluated as per RECIST v1.1.	12 weeks
Secondary	Tumor response as per iRECIST	Response of non-irradiated lesions will be evaluated as per iRECIST	12 weeks
Secondary	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
Secondary	Patient-reported quality of life	Quality of life will be assessed as per EORTC-QLQ C30 questionnaire	12 weeks
Secondary	Systemic immune response	Exploratory translational analyses will be performed using blood and fecal samples	12 weeks