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

Sponsor

University Hospital, Ghent (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03511391

Collaborator

GZA Ziekenhuizen Campus Sint-Augustinus (Other), AZ Sint-Lucas Brugge (Other), Jules Bordet Institute (Other), AZ Sint-Lucas Gent (Other)

Enrollment

Locations

Arms

53.2

Anticipated Duration (Months)

19.8

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Urothelial Carcinoma Melanoma Renal Cell Carcinoma Non-small Cell Lung Cancer Head and Neck Cancer	Drug: Nivolumab or Pembrolizumab or Atezolizumab Radiation: SBRT	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

99 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 9, 2018

Anticipated Primary Completion Date :

Feb 14, 2022

Anticipated Study Completion Date :

Aug 14, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental arm Stereotactic body radiotherapy concurrent with checkpoint inhibitor treatment: Nivolumab or Pembrolizumab or Atezolizumab + SBRT	Drug: Nivolumab or Pembrolizumab or Atezolizumab per national standard of care Other Names: Immune checkpoint inhibitor 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. Other Names: Stereotactic body radiotherapy, SABR, Stereotactic ablative radiotherapy
Active Comparator: Control arm Checkpoint inhibitor treatment only: Nivolumab or Pembrolizumab or Atezolizumab monotherapy	Drug: Nivolumab or Pembrolizumab or Atezolizumab per national standard of care Other Names: Immune checkpoint inhibitor

Arm

Intervention/Treatment

Experimental: Experimental arm

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

Drug: Nivolumab or Pembrolizumab or Atezolizumab

per national standard of care

Other Names:

Immune checkpoint inhibitor

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.

Other Names:

Stereotactic body radiotherapy, SABR, Stereotactic ablative radiotherapy

Active Comparator: Control arm

Checkpoint inhibitor treatment only: Nivolumab or Pembrolizumab or Atezolizumab monotherapy

Drug: Nivolumab or Pembrolizumab or Atezolizumab

per national standard of care

Other Names:

Immune checkpoint inhibitor

Outcome Measures

Primary Outcome Measures

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

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 RECIST [12 weeks]
Response of non-irradiated lesions will be evaluated as per RECIST v1.1.
Tumor response as per iRECIST [12 weeks]
Response of non-irradiated lesions will be evaluated as per iRECIST
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	AZ Sint-Lucas	Ghent	Oost-Vlaanderen	Belgium	9000
2	AZ Sint-Lucas	Brugge	West-Vlaanderen	Belgium	8000
3	GasthuisZusters Antwerpen	Antwerp		Belgium	2000
4	Jules Bordet Institute	Brussels		Belgium	1000
5	University Hospital Ghent	Ghent		Belgium	9000