Prostate CancerPhase 2NCT03061539
Nivolumab and Ipilimumab Treatment in Prostate Cancer With an Immunogenic Signature
A Phase 2 study testing Nivolumab & Ipilimumab in people with Prostate Cancer, run by University College, London at 1 site in United Kingdom.
Trial summary
The primary objective is to test the following hypothesis: Patients with metastatic castrate resistant prostate cancer that have progressed following at least one line of therapy and have an immunogenic signature will respond to combined PD-1 and CTLA4 inhibition. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Nivolumab & Ipilimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 380 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 6 Feb 2018to Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Metastatic castrate resistant prostate cancer.
- Histologically confirmed prostate adenocarcinoma.
- Patient has archival prostate cancer tissue available or is willing to undergo a new biopsy.
- Immunogenic biomarker positive disease - see Appendix 1 NB patients will be included in the trial if they meet all other eligibility criteria. Analysis of the ImS will take place after registration. Patients who do not have ImS positive disease will be withdrawn from the trial.
- WHO performance status of 0-1.
- Adequate haematological status.
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- Adequate liver and renal function.
- Has had 1 or more lines of systemic treatment for mCRPC.
- Documented prostate cancer progression within 6 months prior to screening
- Ongoing androgen deprivation with serum testosterone <1.73 nmol/L.
Who cannot join
- Any history of autoimmune disease, with the exception of patients with a history of autoimmune-related hyperthyroidism or hypothyroidism who are in remission or on a stable dose of thyroid-replacement hormone.
- Patients with prior allogeneic stem cell or solid organ transplantation.
- Active invasive malignancy in the previous 2 years excluding non-melanoma skin cancer.
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan.
- (History of radiation pneumonitis in the radiation field is permitted).
- Patients with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
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- Patients with risk factors for bowel perforation.
- History of grade ≥2 peripheral neuropathy.
- Received therapeutic oral or intravenous (IV) antibiotics within 14 days prior to enrolment (Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or COPD) are eligible).
- Patients must not have had systemic corticosteroid therapy (>10mg daily prednisone equivalent) for 14 days prior to study entry, or concomitant use of other immunosuppressive medications. The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids (i.e., for adrenal insufficiency), and mineralocorticoids (e.g., fludrocortisone) is allowed.
- Prior treatment with Sipuleucel-T, immune checkpoint targeting agents or other novel immune-oncology agents.
- Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study.
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias, or unstable angina.
- Patients with uncontrolled Type 1 diabetes mellitus. Patients controlled on a stable insulin regimen are eligible.
- Patients with uncontrolled adrenal insufficiency.
- Patients with active hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C.
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
Trial locations and contacts
1 site in 1 country.
About this study
The primary objective is to test the following hypothesis: Patients with metastatic castrate resistant prostate cancer that have progressed following at least one line of therapy and have an immunogenic signature will respond to combined PD-1 and CTLA4 inhibition.
Read the detailed description
This is a two-arm non-randomised, non-comparative phase II trial designed to assess the efficacy of nivolumab + ipilimumab in patients with metastatic castrate resistant prostate cancer that have progressed following at least 1 line of therapy and have an specified immunogenic signature. The immunogenic signature is defined by the presence of at least one of the following:
- Mismatch repair deficiency by IHC
- Defective DNA repair detected by a targeted sequencing panel
- High inflammatory infiltrate defined on multiplexed IHC criteria.
Treatment consists of :
Cohort 1:
- Nivolumab 1 mg/kg + ipilimumab 3 mg/kg every three weeks for a maximum of 4 doses
- 6 week gap after last combination dose
- 480 mg flat dose of nivolumab every 4 weeks for up to one year, or until progression, unacceptable toxicity or withdrawal of consent.
Cohort 2:
- Nivolumab 3 mg/kg + ipilimumab 1 mg/kg every three weeks for a maximum of 4 doses
- 3 week gap after last combination dose
- 480 mg flat dose of nivolumab every 4 weeks for up to one year, or until progression, unacceptable toxicity or withdrawal of consent.
Patients must have ongoing androgen deprivation to maintain serum testosterone < 1.73 nmol/L.
- Conditions
- Prostate Cancer
- Being tested
- Nivolumab & Ipilimumab
- Keywords
- Immunogenic signature
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab & IpilimumabDrug
Combination Therapy: Cohort 1: Nivolumab 1 mg/kg + ipilimumab 3 mg/kg every 3 weeks for a maximum of 4 cycles . Cohort 2 : Nivolumab 3mg/kg + ipilimumab 1mg/kg every 3 weeks for a maximum of 4 cycles.
Treatment free gap after last combination dose : Cohort 1: 6 weeks; Cohort 2: 3 weeks
Monotherapy: 480 mg flat dose of nivolumab every 4 weeks for up to 10 cycles, or until progression, unacceptable toxicity or withdrawal of consent
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab & Ipilimumab - Cohort 1 | Experimental | Patients will receive Nivolumab 1 mg/kg + ipilimumab 3 mg/kg every three weeks for a maximum of 4 doses followed by a 6 week gap after last combination dose. The patients will then receive 480 mg flat dose of nivolumab every 4 weeks for up to one year, or until progression, unacceptable toxicity or withdrawal of consent. Receives: Drug: Nivolumab & Ipilimumab |
| Nivolumab & Ipilimumab - Cohort 2 | Experimental | Patients will receive Nivolumab 3 mg/kg + ipilimumab 1 mg/kg every three weeks for a maximum of 4 doses followed by a 3 week gap after last combination dose. The patients will then receive 480 mg flat dose of nivolumab every 4 weeks for up to one year, or until progression, unacceptable toxicity or withdrawal of consent. Receives: Drug: Nivolumab & Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite response rate
Patients will be considered as having had a treatment response if any one of the following criteria are satisfied:
- Radiological response (RECIST 1.1)
- PSA response ≥50% confirmed by a second PSA test at least 4 weeks later (PCWG3 2016)
- Conversion of CTC count from ≥5 cells/7.5ml at baseline to <5 cells/7.5ml confirmed by a second CTC test at least 4 weeks later (PCWG3 2016)
Measured: Up to 5 years following the start of treatment
Secondary outcomes (5)
Overall survival
Measured: From date of registration until the date of first documented date of death from any cause, assessed up to 5 years.
Radiological progression free survival
Measured: From registration to objective disease progression or death from any cause, whichever comes first, assessed up to 5 years
PSA progression free survival
Measured: From registration to PSA progression free survival assessed up to 5 years
Change in patient reported outcome measures (NCI's PRO-CTCAE)
Measured: From registration until 5 years post treatment
Frequency and severity of adverse events
Measured: For 24 months post the start of trial treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2017
- Study start6 Feb 2018
- Primary completion20 Jun 2022
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by University College, LondonThe 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
- Non-randomised
- Intervention model
- Single group
- Model description
- Two-arm non-randomised, non-comparative phase II trial
- Masking
- None (open label)
- Enrolment
- 380 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Dr Mark Linch, Principal investigator, University College London Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03061539
- Sponsor's protocol ID
- CA209-935
- Status last verified
- Jun 2022
- First submitted
- 15 Feb 2017
- Last updated
- 28 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nivolumab and Ipilimumab Treatment in Prostate Cancer With an Immunogenic Signature
- ClinicalTrials.gov ID
- NCT03061539
- Acronym / sponsor ID
- CA209-935
- Conditions
- Prostate Cancer
- Keywords
- Immunogenic signature
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 380 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 6 Feb 2018 (actual)
- Primary completion
- 20 Jun 2022 (actual)
- Study completion
- Jun 2027 (estimated)
- First posted
- 23 Feb 2017 (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.
The primary objective is to test the following hypothesis: Patients with metastatic castrate resistant prostate cancer that have progressed following at least one line of therapy and have an immunogenic signature will respond to combined PD-1 and CTLA4 inhibition.
Detailed description
This is a two-arm non-randomised, non-comparative phase II trial designed to assess the efficacy of nivolumab + ipilimumab in patients with metastatic castrate resistant prostate cancer that have progressed following at least 1 line of therapy and have an specified immunogenic signature. The immunogenic signature is defined by the presence of at least one of the following:
- Mismatch repair deficiency by IHC
- Defective DNA repair detected by a targeted sequencing panel
- High inflammatory infiltrate defined on multiplexed IHC criteria.
Treatment consists of :
Cohort 1:
- Nivolumab 1 mg/kg + ipilimumab 3 mg/kg every three weeks for a maximum of 4 doses
- 6 week gap after last combination dose
- 480 mg flat dose of nivolumab every 4 weeks for up to one year, or until progression, unacceptable toxicity or withdrawal of consent.
Cohort 2:
- Nivolumab 3 mg/kg + ipilimumab 1 mg/kg every three weeks for a maximum of 4 doses
- 3 week gap after last combination dose
- 480 mg flat dose of nivolumab every 4 weeks for up to one year, or until progression, unacceptable toxicity or withdrawal of consent.
Patients must have ongoing androgen deprivation to maintain serum testosterone < 1.73 nmol/L.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Two-arm non-randomised, non-comparative phase II trial
| Arm | Type | Receives |
|---|---|---|
| Nivolumab & Ipilimumab - Cohort 1 | Experimental | Drug: Nivolumab & IpilimumabPatients will receive Nivolumab 1 mg/kg + ipilimumab 3 mg/kg every three weeks for a maximum of 4 doses followed by a 6 week gap after last combination dose. The patients will then receive 480 mg flat dose of nivolumab every 4 weeks for up to one year, or until progression, unacceptable toxicity or withdrawal of consent. |
| Nivolumab & Ipilimumab - Cohort 2 | Experimental | Drug: Nivolumab & IpilimumabPatients will receive Nivolumab 3 mg/kg + ipilimumab 1 mg/kg every three weeks for a maximum of 4 doses followed by a 3 week gap after last combination dose. The patients will then receive 480 mg flat dose of nivolumab every 4 weeks for up to one year, or until progression, unacceptable toxicity or withdrawal of consent. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Metastatic castrate resistant prostate cancer.
- Histologically confirmed prostate adenocarcinoma.
- Patient has archival prostate cancer tissue available or is willing to undergo a new biopsy.
- Immunogenic biomarker positive disease - see Appendix 1 NB patients will be included in the trial if they meet all other eligibility criteria. Analysis of the ImS will take place after registration. Patients who do not have ImS positive disease will be withdrawn from the trial.
- WHO performance status of 0-1.
Key exclusion criteria (17 listed)
- Any history of autoimmune disease, with the exception of patients with a history of autoimmune-related hyperthyroidism or hypothyroidism who are in remission or on a stable dose of thyroid-replacement hormone.
- Patients with prior allogeneic stem cell or solid organ transplantation.
- Active invasive malignancy in the previous 2 years excluding non-melanoma skin cancer.
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan.
- (History of radiation pneumonitis in the radiation field is permitted).
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 & IpilimumabCombination Therapy: Cohort 1: Nivolumab 1 mg/kg + ipilimumab 3 mg/kg every 3 weeks for a maximum of 4 cycles . Cohort 2 : Nivolumab 3mg/kg + ipilimumab 1mg/kg every 3 weeks for a maximum of 4 cycles. Treatment free gap after last combination dose : Cohort 1: 6 weeks; Cohort 2: 3 weeks Monotherapy: 480 mg flat dose of nivolumab every 4 weeks for up to 10 cycles, or until progression, unacceptable toxicity or withdrawal of consent | Drug | Nivolumab & Ipilimumab - Cohort 1, Nivolumab & Ipilimumab - Cohort 2 |
Primary outcome
Composite response rate
Time frame: Up to 5 years following the start of treatment
Patients will be considered as having had a treatment response if any one of the following criteria are satisfied: * Radiological response (RECIST 1.1) * PSA response ≥50% confirmed by a second PSA test at least 4 weeks later (PCWG3 2016) * Conversion of CTC count from ≥5 cells/7.5ml at baseline to <5 cells/7.5ml confirmed by a second CTC test at least 4 weeks later (PCWG3 2016)
5 secondary outcomes
Overall survival
Time frame: From date of registration until the date of first documented date of death from any cause, assessed up to 5 years.
Radiological progression free survival
Time frame: From registration to objective disease progression or death from any cause, whichever comes first, assessed up to 5 years
PSA progression free survival
Time frame: From registration to PSA progression free survival assessed up to 5 years
Change in patient reported outcome measures (NCI's PRO-CTCAE)
Time frame: From registration until 5 years post treatment
Frequency and severity of adverse events
Time frame: For 24 months post the start of trial treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2022.
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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.
Dr Mark Linch principal investigator
University College London Hospitals
1 site 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 & Ipilimumab in people with Prostate Cancer, run by University College, London at 1 site in United Kingdom.
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 10 inclusion and 17 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: under way, not looking for participants, as of the sponsor's last update on 28 Sep 2022. 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 United Kingdom. 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?
This study is still under way. Results are not available in the source record yet.
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?
Composite response rate (time frame: Up to 5 years following the start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Sep 2022.