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

NCT ID: NCT03511391

Last Updated: 2024-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 99 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-09
• Study Completion Date: 2024-01-23

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental arm

Stereotactic body radiotherapy concurrent with checkpoint inhibitor treatment:

Nivolumab or Pembrolizumab or Atezolizumab + SBRT

Group Type: EXPERIMENTAL

Nivolumab or Pembrolizumab or Atezolizumab

Intervention Type: DRUG

per national standard of care

SBRT

Intervention Type: RADIATION

Stereotactic body radiotherapy is administered to maximally 3 lesions in 3 fractions of 8Gy prior to the second/third cycle of checkpoint inhibitors.

Control arm

Checkpoint inhibitor treatment only:

Nivolumab or Pembrolizumab or Atezolizumab monotherapy

Group Type: ACTIVE_COMPARATOR

Nivolumab or Pembrolizumab or Atezolizumab

Intervention Type: DRUG

per national standard of care

Interventions

Nivolumab or Pembrolizumab or Atezolizumab

per national standard of care

Intervention Type: DRUG

SBRT

Stereotactic body radiotherapy is administered to maximally 3 lesions in 3 fractions of 8Gy prior to the second/third cycle of checkpoint inhibitors.

Intervention Type: RADIATION

Other Intervention Names

Immune checkpoint inhibitor; Stereotactic body radiotherapy, SABR, Stereotactic ablative radiotherapy

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GZA Ziekenhuizen Campus Sint-Augustinus

OTHER

Sponsor Role: collaborator

AZ Sint-Lucas Brugge

OTHER

Sponsor Role: collaborator

Jules Bordet Institute

OTHER

Sponsor Role: collaborator

AZ Sint-Lucas Gent

OTHER

Sponsor Role: collaborator

University Hospital, Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Piet Ost, PhD

Role: PRINCIPAL_INVESTIGATOR

University Ghent

Locations

AZ Sint-Lucas

Ghent, Oost-Vlaanderen, Belgium

AZ Sint-Lucas

Bruges, West-Vlaanderen, Belgium

GasthuisZusters Antwerpen

Antwerp, , Belgium

Jules Bordet Institute

Brussels, , Belgium

University Hospital Ghent

Ghent, , Belgium

Countries

Belgium

References

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.

Reference Type: RESULT

PMID: 37410476 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33962592 (View on PubMed)

Other Identifiers

EC2017/1678

Identifier Type: -

Identifier Source: org_study_id