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Prostate Cancer MetastaticPhase 2CheckPRONCT05655715

Checkpoint Inhibitors and SBRT for MCRPC

A Phase 2 study testing Stereotactic body radiotherapy, Ipilimumab Injection [Yervoy] and Nivolumab Injection [Opdivo] in people with Prostate Cancer Metastatic and Castrate Resistant Prostate Cancer, run by Herlev and Gentofte Hospital at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The goal of this investigator-initiated, single-center, and randomized phase II trial is to investigate the potential synergistic effect of combining stereotactic body radiotherapy of a single soft tissue- or bone metastasis with ipilimumab and nivolumab in patients with mCRPC and perform translational analyses on… Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Stereotactic body radiotherapy, Ipilimumab Injection [Yervoy] and Nivolumab Injection [Opdivo]
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
1 siteDenmark
Study dates
25 Nov 2019to 30 Aug 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
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Have a signed Independent Ethics Committee (IEC)-approved informed consent form prior to any study-specific evaluation. Subjects must be willing and able to comply with scheduled visits, treatment schedule, lab testing and other requirements of the study.
  • Male ≥18 years of age at the time consent form is signed
  • Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate (pure small-cell histology or pure high-grade neuroendocrine histology are excluded; neuroendocrine differentiation is allowed)
  • If possible, metastases accessible for image-guided percutaneous biopsy should be performed, if considered safe assessed by the PI.
  • Surgically or medically castrated, with serum testosterone levels <50 ng/dL (1.73 nM). For patients currently being treated with luteinizing hormone-releasing hormone (LHRH) agonists (i.e., patients who have not undergone an orchiectomy) therapy must be continued throughout the study
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
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  • Life expectancy greater than 3 months
  • Evidence of disease progression after prior therapy for mCRPC:
  • Disease progression after treatment with 1 androgen-receptor (AR) targeted therapies (abiraterone acetate, enzalutamide or investigational AR-targeted drug) for castrate-resistant disease AND
  • Disease progression after treatment with 1 line of taxane-based chemotherapy for castration resistant disease. Prior taxane therapy administered for hormone sensitive disease is permitted and is not counted toward this limit.
  • Disease progression after initiation of most recent therapy is based on any of the following criteria:
  • Rise in PSA: a minimum of 2 consecutive rising levels, with an interval of ≥ 1 week between each determination. The most recent screening measurement must have been ≥ 2ng/mL
  • Transaxial imaging: New or progressive tumor on CT or MRI scans as defined by RECIST 1.1 or new lesions on bone scan per PCWG3.
  • Have adequate organ function confirmed by the following laboratory values obtained within 14 days prior to the first dose of immunotherapy with nivolumab and ipilimumab:
  • Bone marrow function: i. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L ii. Platelets > 100 x 109/L iii. Hemoglobin ≥ 9 g/dL (5.6 mmol/L) independent of transfusion within 14 days b. Hepatic function: i. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN). For patients with liver metastases AST and ALT < 5 x ULN ii. Bilirubin < 1.5 x ULN c. Renal function: Serum creatinine < 1.5 x ULN d. Coagulations status: International Normalized Ratio (INR) ≤ 1.5
  • Male patients with female partners of childbearing potential may be enrolled if they are:
  • Documented to be surgically sterile (ie, vasectomy): or
  • Committed to practicing true abstinence during treatment and for 4 months after the last dose of immunotherapy; or
  • Committed to using any contraception method with a failure rate of less than 1% per year of contraception (refer to protocol) with their partner during treatment and for 4 months following last dose of immunotherapy.

Who cannot join

  • Active malignancy, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or superficial bladder cancer
  • Patients with a history of malignancy that has been completely treated, and currently with no evidence of that cancer, are permitted to be enrolled in the trial provided all chemotherapy was completed > 6 months prior and/or bone marrow transplant > 2years prior to first dose of ipilimumab and nivolumab
  • Prior therapy with an anti-programmed cell death protein 1 (anti-PD1), anti-programmed death-ligand 1 (anti-PD-L1), anti-CD137 or anti-CTLA4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
  • Symptomatic and/or untreated central nervous system (CNS) metastases. Patients with asymptomatic, previously treated CNS metastases are eligible provided they have been clinically stable (i.e., not requiring steroids for at least 4 weeks prior to first dose of ipilimumab and nivolumab and have had appropriate scans screening assessments)
  • Symptomatic or impending spinal cord compression unless appropriately treated, clinically stable and asymptomatic
  • If patient have an active known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type 1 diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur in the absence of an external trigger
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  • Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or history of chronic hepatitis B or C
  • Received treatment with chemotherapy, hormonal therapy (with the exception of LHRH analog), radiation, antibody therapy or immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors or experimental drugs within 4 weeks prior to first dose of ipilimumab and nivolumab
  • Adverse effect of prior therapy not resolved to CTCAE Grade 1 or below with the exception of alopecia. Ongoing Grade 2 non-hematologic toxicity related to most recent treatment regimen may be permitted with prior advanced approval from the sponsor
  • Initiated denosumab or bisphosphonate therapy or adjusted denosumab or bisphosphonate dose/regimen within 4 weeks prior to first dose of ipilimumab and nivolumab. Patients on stable denosumab or bisphosphonate regimen are eligible and may continue treatment
  • Non-study related minor surgery procedure <5 days or major surgery < 21 days prior to first dose of ipilimumab and nivolumab; in all cases the patient must be sufficiently recovered and stable before treatment administration
  • Presence of auto-immune diseases
  • Presence of any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results, and in the opinion of the investigator would make the patient inappropriate for entry into the study
  • Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids ( >10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • As there is a potential risk for hepatic toxicity with nivolumab/ipilimumab combinations, drugs with a predisposition to hepatotoxicity should be used with caution in patients treated with nivolumab/ipilimumab containing regimen
  • Allergies
  • History of allergy to study drug components
  • History of severe hypersensitivity reaction to any monoclonal antibody

Trial locations and contacts

1 site in 1 country.

Denmark1 site

  • Department of Oncology, Copenhagen University Hospital Herlev and Gentofte Hospital

    Herlev, Capital Region, 2730

Other trials in Denmark

About this study

Official title: Randomised Phase 2 Trial of Stereotactic Body Radiation Therapy, SBRT in Combination with Checkpoint Inhibitors in Metastatic Castration-resistant Prostate Cancer

The goal of this investigator-initiated, single-center, and randomized phase II trial is to investigate the potential synergistic effect of combining stereotactic body radiotherapy of a single soft tissue- or bone metastasis with ipilimumab and nivolumab in patients with mCRPC and perform translational analyses on tissue and blood, searching for predictive biomarkers of efficacy and toxicity.

Participants will be randomized to receive ipilimumab and nivolumab with or without stereotactic body radiotherapy (SBRT).

Read the detailed description

The participants receive treatment for 52 weeks, including four cycles of ipilimumab and nivolumab with or without concomitant SBRT (24 Gray in three fractions) to a single soft tissue or bone metastasis, followed by 10 cycles of nivolumab. Participants are followed until progression, death, or for 12 months after the end of treatment.

Biopsies from metastatic sites are collected at baseline, before the third treatment, and at the end of treatment. Blood sampling for immune monitoring and circulating tumor DNA is performed consecutively at baseline and every radiographic assessment.

Being tested
Stereotactic body radiotherapy, Ipilimumab Injection [Yervoy], Nivolumab Injection [Opdivo], Biopsies
Keywords
Oncology, metastatic castration-resistant prostate cancer, Immunotherapy, Stereotactic body radiotherapy, Translational research, Prostate cancer
Medical subject headings
Prostatic Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Stereotactic body radiotherapyRadiation

    Also called 8 Gray x 3

    8 Gray x 3

  • Ipilimumab Injection [Yervoy]Drug

    Also called ipi

    1 mg/kg IV Q3W for four doses,

  • Nivolumab Injection [Opdivo]Drug

    Also called nivo

    Nivolumab 3mg/kg IV Q3W for four doses, then then Nivolumab 480mg IV Q4W

  • BiopsiesProcedure or surgery

    From soft tissue metastases.

Study groups in NCT05655715
Study groupRoleWhat they receive
A SBRT + ipi/nivoExperimentalStereotactic body radiotherapy of 8 Gray (Gy) x 3 on one soft tissue or bone metastasis + Nivolumab 3mg/kg IV every 3 weeks (Q3W) + Ipilimumab 1mg/kg IV Q3W for four doses, then Nivolumab 480 mg IV every 4 weeks (Q4W) for up to 52 weeks treatment in total
Receives: Radiation: Stereotactic body radiotherapy; Drug: Ipilimumab Injection [Yervoy]; Drug: Nivolumab Injection [Opdivo]; Procedure: Biopsies
B ipi/nivoExperimentalNivolumab 3mg/kg IV Q3W + Ipilimumab 1mg/kg IV Q3W for four doses, then Nivolumab 480 mg IV Q4W for up to 52 weeks treatment in total
Receives: Drug: Ipilimumab Injection [Yervoy]; Drug: Nivolumab Injection [Opdivo]; Procedure: Biopsies

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Co-primary endpoint 1

    Objective response rate (ORR) according to modified Response Evaluation Criteria in Solid Tumours (RECIST1.1) per Prostate Cancer Clinical Trials Working Group (PCWG3) criteria for patients with measurable disease

    Measured: From baseline until progression (up to 24 months)

  2. Co-primary endpoint 2

    Prostate-specific antigen (PSA) response rate of ≥ 50% decline from baseline at any time from treatment start (confirmed after ≥ 4 weeks, all patients with measurable and non-measurable disease)

    Measured: Any time after treatment start (confirmed ≥ 3 weeks later, up to 24 months)

Secondary outcomes (7)

  1. Adverse events (Safety)

    Common Terminology Criteria for Adverse Events (CTCAE) v. 5

    Measured: From inclusion to 100 days after the last dose of ipilimumab or nivolumab or until the last study visit (up to 24 months)

  2. Radiographic progression-free survival

    Per PCWG3 with 2+2 rule and clinical progression (all patients)

    Measured: From baseline until progression (up to 24 months)

  3. Clinical benefit rate

    Per RECIST 1.1 and Immune Response Evaluation Criteria in Solid Tumours (iRECIST)

    Measured: From baseline until progression (up to 24 months)

  4. Objective response rate (ORR)

    Per iRECIST

    Measured: From baseline until progression (up to 24 months)

  5. PSA progression-free survival

    Per PCWG3

    Measured: beyond 12 weeks (up to 24 months)

  6. Survival

    Overall survival

    Measured: From randomization until death by any cause or last follow-up (up to 24 months)

  7. European Organization for Research and Treatment of Cancer Quality of life of cancer patients (EORTC QLQ-C30)

    Questionaire The EORTC QLQ-C30 is a validated questionnaire to assess the quality of life of cancer patients. It includes 30 questions, divided into three major dimensions of global health status, functional-, and symptoms scale. The scales are calculated into a score ranging from 0-100. A high score on global health status and functional scales represents a better quality of life, but a high score on the symptoms scale represents a high burden of symptoms/low quality of life.

    Measured: Baseline and then every 8 weeks (up to three times) until end-of-treatment (up to 24 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Dec 2022
  2. Study start25 Nov 2019
  3. Primary completion30 Aug 2024
  4. Study completion30 Aug 2024

Resources

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
Model description
Two experimental treatment arms.
Masking
None (open label)
Enrolment
90 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05655715
Sponsor's protocol ID
UR1840
Acronym
CheckPRO
Status last verified
Oct 2024
First submitted
7 Dec 2022
Last updated
16 Oct 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: According to International Committee of Medical Journal Editors (ICMJE) guideline: Will individual participant data be available (including data dictionaries)? No. What data in particular will be shared? None. What other documents will be available? Study Protocol, Statistical Analysis Plan, analytic software code. When will data be available (start and end dates)? The study protocol is available from the beginning of the trial. Statistical analysis plan and analytic code will be available beginning 3 months and ending 5 years following the article publication of the primary endpoint. With whom? Investigators who state their purpose. For what types of analyses? Any By what mechanism will data be made available? Proposals should be directed to the PI.

Publications

  • Eefsen RL, Spindler NJ, Theile S, Al-Farra G, Hendel HW, Lorentzen T, Fredberg Persson G, Behrens CP, Chen IM, Madsen K, Sengelov L, Svane IM, Lindberg H, Kongsted P, Nielsen DL. Randomized phase II trial of nivolumab and ipilimumab with or without stereotactic body radiation therapy in patients with metastatic castration-resistant prostate cancer: the CheckPRO, CA209-8TY trial. J Immunother Cancer. 2026 Jul 23;14(7):e014803. doi: 10.1136/jitc-2026-014803.

    PubMed 42493213

  • Spindler NJ, Persson GF, Theile S, Nielsen DL, Hogdall EV, Al-Farra G, Hendel HW, Lorentzen T, Svane IM, Lindberg H, Eefsen RL. Randomised phase II trial of stereotactic body radiotherapy in combination with checkpoint inhibitors in metastatic castration-resistant prostate cancer (CheckPRO): a study protocol. BMJ Open. 2023 Jan 30;13(1):e063500. doi: 10.1136/bmjopen-2022-063500.

    PubMed 36717150

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Stereotactic body radiotherapy, Ipilimumab Injection [Yervoy] and Nivolumab Injection [Opdivo] in people with Prostate Cancer Metastatic and Castrate Resistant Prostate Cancer, run by Herlev and Gentofte Hospital at 1 site in Denmark.

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 19 inclusion and 18 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 16 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. 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?

Co-primary endpoint 1 (time frame: From baseline until progression (up to 24 months)). The study lists 2 primary outcomes in all. 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 NCT05655715, 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 16 Oct 2024.

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