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

Phase 2

Completed

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

• Registration Number: NCT03511391
• Lead Sponsor: University Hospital, Ghent

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-03-09
• Study First Submitted: 2018-04-17
• Study First Submitted QC: 2018-04-17
• Study First Posted: 2018-04-27
• Primary Completion: 2022-02-01
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-22
• Study Completion: 2024-01-23
• Last Update Posted: 2024-01-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 99

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental arm	SBRT	Stereotactic body radiotherapy concurrent with checkpoint inhibitor treatment: Nivolumab or Pembrolizumab or Atezolizumab + SBRT
Control arm	Nivolumab or Pembrolizumab or Atezolizumab	Checkpoint inhibitor treatment only: Nivolumab or Pembrolizumab or Atezolizumab monotherapy
Experimental arm	Nivolumab or Pembrolizumab or Atezolizumab	Stereotactic body radiotherapy concurrent with checkpoint inhibitor treatment: Nivolumab or Pembrolizumab or Atezolizumab + SBRT

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (4)

University Hospital Ghent; 🇧🇪 Ghent, Belgium

AZ Sint-Lucas; 🇧🇪 Brugge, West-Vlaanderen, Belgium

GasthuisZusters Antwerpen; 🇧🇪 Antwerp, Belgium

Jules Bordet Institute; 🇧🇪 Brussels, Belgium