Urothelial CarcinomaPhase 2CHEERSNCT03511391
CHEckpoint Inhibition in Combination With an Immunoboost of External Beam Radiotherapy in Solid Tumors
A Phase 2 study testing Nivolumab or Pembrolizumab or Atezolizumab and SBRT in people with Urothelial Carcinoma and Melanoma, run by University Hospital, Ghent at 5 sites in Belgium.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Carcinoma, Melanoma, Renal Cell Carcinoma
- What is being tested?
- Nivolumab or Pembrolizumab or Atezolizumab and SBRT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 99 participants
- Where
- 5 sitesBelgium
- Study dates
- 9 Mar 2018to 23 Jan 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Belgium5 sites
GasthuisZusters Antwerpen
Antwerp, 2000
AZ Sint-Lucas
Bruges, West-Vlaanderen, 8000
Jules Bordet Institute
Brussels, 1000
AZ Sint-Lucas
Ghent, Oost-Vlaanderen, 9000
University Hospital Ghent
Ghent, 9000
About this study
Official title: CHEckpoint Inhibition in Combination With an Immunoboost of External Beam Radiotherapy in Solid Tumors: CHEERS-trial
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
- Being tested
- Nivolumab or Pembrolizumab or Atezolizumab, SBRT
- Keywords
- radiotherapy, checkpoint inhibitors
- Medical subject headings
- Carcinoma, Transitional Cell, Melanoma, Carcinoma, Renal Cell, Carcinoma, Non-Small-Cell Lung, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab or Pembrolizumab or AtezolizumabDrug
Also called Immune checkpoint inhibitor
per national standard of care
SBRTRadiation
Also called Stereotactic body radiotherapy, SABR, Stereotactic ablative radiotherapy
Stereotactic body radiotherapy is administered to maximally 3 lesions in 3 fractions of 8Gy prior to the second/third cycle of checkpoint inhibitors.
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm | Experimental | Stereotactic body radiotherapy concurrent with checkpoint inhibitor treatment:
Nivolumab or Pembrolizumab or Atezolizumab + SBRT Receives: Drug: Nivolumab or Pembrolizumab or Atezolizumab; Radiation: SBRT |
| Control arm | Active comparator | Checkpoint inhibitor treatment only:
Nivolumab or Pembrolizumab or Atezolizumab monotherapy Receives: Drug: Nivolumab or Pembrolizumab or Atezolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 15 months
Secondary outcomes (6)
Overall survival
Overall survival will be defined as the time from randomization to death from any cause.
Measured: 2 years after start trial treatment
Tumor response as per RECIST
Response of non-irradiated lesions will be evaluated as per RECIST v1.1.
Measured: 12 weeks
Tumor response as per iRECIST
Response of non-irradiated lesions will be evaluated as per iRECIST
Measured: 12 weeks
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
Measured: 12 weeks
Patient-reported quality of life
Quality of life will be assessed as per EORTC-QLQ C30 questionnaire
Measured: 12 weeks
Systemic immune response
Exploratory translational analyses will be performed using blood and fecal samples
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2018
- Study start9 Mar 2018
- Primary completion1 Feb 2022
- Study completion23 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by University Hospital, GhentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Ghent
- Sponsor type
- University, hospital or other
- Collaborators
- GZA Ziekenhuizen Campus Sint-Augustinus, AZ Sint-Lucas Brugge, Jules Bordet Institute, AZ Sint-Lucas Gent
- Responsible party
- Sponsor
- Investigators
- Piet Ost, PhD, Principal investigator, University Ghent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03511391
- Sponsor's protocol ID
- EC2017/1678
- Acronym
- CHEERS
- Status last verified
- Jan 2024
- First submitted
- 17 Apr 2018
- Last updated
- 23 Jan 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37410476Spaas 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.
PubMed 33962592
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CHEckpoint Inhibition in Combination With an Immunoboost of External Beam Radiotherapy in Solid Tumors: CHEERS-trial
- ClinicalTrials.gov ID
- NCT03511391
- Acronym / sponsor ID
- CHEERS / EC2017/1678
- Conditions
- Urothelial Carcinoma, Melanoma, Renal Cell Carcinoma, Non-small Cell Lung Cancer, Head and Neck Cancer
- Keywords
- radiotherapy, checkpoint inhibitors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 99 participants (actual)
- Lead sponsor
- University Hospital, GhentUniversity, hospital or other
- Collaborators
- GZA Ziekenhuizen Campus Sint-Augustinus, AZ Sint-Lucas Brugge, Jules Bordet Institute, AZ Sint-Lucas Gent
- Study start
- 9 Mar 2018 (actual)
- Primary completion
- 1 Feb 2022 (actual)
- Study completion
- 23 Jan 2024 (actual)
- First posted
- 27 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental arm | Experimental | Drug: Nivolumab or Pembrolizumab or Atezolizumab, Radiation: SBRTStereotactic body radiotherapy concurrent with checkpoint inhibitor treatment: Nivolumab or Pembrolizumab or Atezolizumab + SBRT |
| Control arm | Active comparator | Drug: Nivolumab or Pembrolizumab or AtezolizumabCheckpoint inhibitor treatment only: Nivolumab or Pembrolizumab or Atezolizumab monotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nivolumab or Pembrolizumab or AtezolizumabAlso: Immune checkpoint inhibitorper national standard of care | Drug | Control arm, Experimental arm |
| SBRTAlso: Stereotactic body radiotherapy, SABR, Stereotactic ablative radiotherapyStereotactic body radiotherapy is administered to maximally 3 lesions in 3 fractions of 8Gy prior to the second/third cycle of checkpoint inhibitors. | Radiation | Experimental arm |
Primary outcome
Progression-free survival
Time frame: 15 months
Progression-free survival will be defined as the time from randomization to disease progression (as per iRECIST) or death from any cause.
6 secondary outcomes
Overall survival
Time frame: 2 years after start trial treatment
Tumor response as per RECIST
Time frame: 12 weeks
Tumor response as per iRECIST
Time frame: 12 weeks
Incidence of Treatment-Related Adverse Events [safety and tolerability]
Time frame: 12 weeks
Patient-reported quality of life
Time frame: 12 weeks
Systemic immune response
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2024.
- Results publication: PubMed 37410476Spaas 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.
- Derived from this study: PubMed 33962592Spaas 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Piet Ost, PhD principal investigator
University Ghent
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab or Pembrolizumab or Atezolizumab and SBRT in people with Urothelial Carcinoma and Melanoma, run by University Hospital, Ghent at 5 sites in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (time frame: 15 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03511391, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2024.