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

NCT03511391 | Completed Phase 2

• 1 other identifier: EC2017/1678
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 5

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

Keywords

radiotherapy; checkpoint inhibitors

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Overall survival

  2 years after start trial treatment

• Tumor response as per RECIST

  12 weeks

• Tumor response as per iRECIST

  12 weeks

• Incidence of Treatment-Related Adverse Events [safety and tolerability]

  12 weeks

• Patient-reported quality of life

  12 weeks

Study Arms (2)

Experimental arm

EXPERIMENTAL

Stereotactic body radiotherapy concurrent with checkpoint inhibitor treatment: Nivolumab or Pembrolizumab or Atezolizumab + SBRT

Drug: Nivolumab or Pembrolizumab or Atezolizumab; Radiation: SBRT

Control arm

ACTIVE COMPARATOR

Checkpoint inhibitor treatment only: Nivolumab or Pembrolizumab or Atezolizumab monotherapy

Drug: Nivolumab or Pembrolizumab or Atezolizumab

Interventions

Nivolumab or Pembrolizumab or Atezolizumab DRUG

per national standard of care

Also known as: Immune checkpoint inhibitor

Control arm; Experimental arm

SBRT RADIATION

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

Also known as: Stereotactic body radiotherapy, SABR, Stereotactic ablative radiotherapy

Experimental arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Ghent: lead
• GZA Ziekenhuizen Campus Sint-Augustinus: collaborator
• AZ Sint-Lucas Brugge: collaborator
• Jules Bordet Institute: collaborator
• AZ Sint-Lucas Gent: collaborator

Study Sites (5)

AZ Sint-Lucas

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

AZ Sint-Lucas

Bruges, West-Vlaanderen, 8000, Belgium

Location

GasthuisZusters Antwerpen

Antwerp, 2000, Belgium

Location

Jules Bordet Institute

Brussels, 1000, Belgium

Location

University Hospital Ghent

Ghent, 9000, Belgium

Location

Related Publications (2)

• 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.

  PMID: 37410476 RESULT

• 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.

  PMID: 33962592 DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Melanoma; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Head and Neck Neoplasms

Interventions

Nivolumab; pembrolizumab; atezolizumab; Immune Checkpoint Inhibitors; Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Piet Ost, PhD

  University Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2018
• First Posted: April 27, 2018
• Study Start: March 9, 2018
• Primary Completion: February 1, 2022
• Study Completion: January 23, 2024
• Last Updated: January 23, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

BE (5)