Prostate CancerPhase 2ImmunoProstNCT03040791
Nivolumab in Prostate Cancer With DNA Repair Defects (ImmunoProst Trial)
A Phase 2 study testing Nivolumab in people with Prostate Cancer, run by Hospital Moinhos de Vento at 2 sites in Brazil.
Trial summary
Prostate Cancer (PC) is the most frequent cancer in men, accounting for 21% of new cases of cancer in men in the United States. Among the four most incident tumors (breast, lung and colorectal cancer); prostate cancer is the only that does not have any predictive biomarker to guide the treatment. 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
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 2 sitesBrazil
- Study dates
- 1 Jun 2018to 1 Mar 2022
- 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
- Histologically confirmed adenocarcinoma of the prostate with tumor tissue available for molecular analyses. If archival tissue for biomarker analysis is not available then the patient must be willing to have a further biopsy to obtain tumor tissue for histological diagnosis.
- Metastatic Castrate-resistant prostate cancer (mCRPC), defined by:
- Disease progression despite androgen deprivation therapy (ADT) and may present as either a continuous rise in serum prostate-specific antigen (PSA) levels, the progression of pre-existing disease, and/or the appearance of new metastases.
- Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nM). If the patient is being treated with GnRH or LHRH agonists or antagonists (patient who have not undergone orchiectomy), this therapy should be maintained.
- Documented prostate cancer progression, during treatment with Docetaxel, as assessed by the investigator with one of the following:
- PSA progression is defined according the PCWG3 criteria: PSA increase, that is ≥ 50% and ≥ 2 ng/mL above the nadir, and which is confirmed by a second value ≥ 3 weeks later (confirmed the rising trend).
Show all 26Show fewer
- Radiographic progression of visceral lesions or soft tissue disease by modified RECIST 1.1 criteria.
- Progression of bone metastasis is defined according the Appendix B: Prostate Cancer Clinical Trials Working Group 3 (Adapted) two or more documented new bone lesions on a bone scan with or without PSA progression. Confirmation of ambiguous results by other imaging modalities (eg, CT or MRI) is obligatory. If Docetaxel chemotherapy is used more than once, this will be considered as one regimen.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 Appendix A: Performance Status Criteria
- Life expectancy > 24 weeks.
- Age ≥ 18 years
- At least 28 days since the completion of any prior anti-cancer therapy (except for LHRH agonists or antagonists), including chemotherapy (taxane-based). Additionally, clinically relevant treatment toxicities should have resolved to grade 1 or less prior to start study treatment.
- For hormonal treatment must be followed the guideline below:
- No antiandrogens are allowed during the study period. The use of antiandrogens before study entry is permitted, but at least 28 days since the completion of prior antiandrogen are required (washout period).
- Corticosteroids dose > Prednisolone 10 mg/day (or equivalent) are allowed only if clinically indicated for medical conditions. At least 28 days since the completion of prior corticotherapy are required (washout period).
- Agreeable to have all the biomarker studies including the fresh tumor biopsies if needed.
- Patients must have adequate organ function within 1 weeks prior enrollment to and evidenced by:
- Hemoglobin ≥ 9.0 g/dL
- WBC > 2.000/mm3
- Absolute neutrophil count ≥ 1.500/mm3
- Platelet count ≥ 100.000/mm3
- Creatinine Clearance ≥ 30 mL/min. Creatinine Clearance (CrCl) must be calculated at screening using the Cockcroft-Gault formula:
- Bilirubin < 3 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome.
- Aspartate transaminase (AST) (SGOT) < 3.0 x ULN.
- Alanine transaminase (ALT) (SGPT) < 3.0 x ULN.
- No cardiac disease defined by as active angina, symptomatic congestive heart failure, or myocardial infarction within previous six months.
Who cannot join
- Patients with any active known or suspected autoimmune disease. Patients with vitiligo, type I diabetes mellitus, controlled autoimmune hypothyroidism, psoriasis not requiring systemic treatment, or other conditions under control are permitted to enroll.
- Patients with conditions that needs systemic corticosteroids dose > Prednisolone 10 mg/day (or equivalent) or other immunosuppressive medications within 28 days prior to the first dose of study drug. Inhaled steroids are permitted if necessary.
- Patients with any known active chronic liver disease.
- Patients who have prior history of malignancy treated with curative intention in the past 2 years with the exception of basal cell carcinoma and squamous cell carcinoma of the skin, which were allowed in any case. Patients with other malignancies that do not fulfill the prior criteria could be considered for recruitment if they do not represent a competitive cause of death and have a low potential to progress to metastatic progression. Patients in this condition may be enrolled in the trial if approved after review by principal investigator.
- Known history of testing positive for human immunodeficiency virus (HIV), known acquired immunodeficiency syndrome (AIDS), or any positive test for hepatitis B or hepatitis C virus representing acute or chronic disease.
- Preceding treatment with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- Major surgery less than 28 days prior to the first dose of study drug.
- Radiation therapy less than 14 days prior to the first dose of study drug.
Trial locations and contacts
2 sites in 1 country.
Brazil2 sites
Hospital Moinhos de Vento
Porto Alegre, Rio Grande do Sul, 90035000
Instituto do Câncer do Estado de São Paulo
São Paulo, São Paulo, 01246000
About this study
Prostate Cancer (PC) is the most frequent cancer in men, accounting for 21% of new cases of cancer in men in the United States. Among the four most incident tumors (breast, lung and colorectal cancer); prostate cancer is the only that does not have any predictive biomarker to guide the treatment. Even though the molecular heterogeneity of PC is well-documented, treatment has not been molecularly stratified and the need for genetic prognostic and predictive markers is critical.
DNA repair defects (DRD), mainly in the Homologous Recombination (HR) pathway (such as BRCA1, BRCA2, ATM and CHEK2) are emerging as potential biomarkers in prostate cancer. It is well known BRCA1 and BRCA2 carriers have better Progression-Free Survival (PFS) and Overall Survival (OS) than non-carriers in ovarian cancer. Differently than ovarian tumors that BRCA mutations provides a good prognosis, PC patients who harbor HR defects have a higher Gleason score 6, an increased risk of recurrence and poor prognosis. The predictive role of DRD in PC was demonstrated in a recent trial using Olaparib, a PARP inhibitor, in DRD carriers. This trial showed 88% of response rate with Olaparib, a PARP inhibitor that acts in HR pathway by synthetic lethality.
Read more
Recent data demonstrated important association between HR deficient high-grade serous ovarian cancer (HGSOC), high neoantigen load and high expression of PD-1/PD-L1 compared with HR proficient HGSOCs 10. This study showed that BRCA1 and BRCA2 mutations increase the number of tumor-infiltrating lymphocytes (TILs) and confer a better prognosis. The unprecedented success of immunotherapy in malignant disorders has provided evidence that the patient's immune system can be improved to attack established tumors, mainly melanoma, non-small cell lung cancer and kidney cancer. A high mutational burden increases the likelihood of the development of specific neoepitopes that would confer clinical benefit from CTLA-4 and PD-1 blockade.
These data showed that specific DNA repair defects increase the mutational burden, the expression of PD-1/PD-L1 and TILs; and could improve the response to immunotherapy in cancer. This rationale was already tested in a trial that evaluated the PD-1 checkpoint inhibitor Pembrolizumab in mismatch-repair deficient patients, a kind of DNA repair defect by definition. This important trial showed that this DRD predicted clinical benefit of immune checkpoint blockade in many types of cancer, especially colorectal cancer.
Read the detailed description
This is a Phase II, two-stage, multi-center, single-arm, and open-label trial of Nivolumab (BMS-936558) in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed to a taxane-based chemotherapy regimen previously. Eligible patients must have ECOG 0-2 and material for biomarker analysis. Prior enzalutamide, abiraterone and cabazitaxel are permitted but not necessary to enrollment. The germline and somatic DRD (BRCA1, BRCA2, ATM, PTEN, CHEK2, RAD51C, RAD51D, PALB2, MLH1, MSH2, MSH6, PMS2.) will be assessed by T-NGS of metastatic sites or by liquid biopsy. The primary endpoint is PSA 50 response rate (PSA50, following the Prostate Cancer Working Group 3 criteria). The trial will meet its endpoint if ≥ 3/29 men achieve a PSA50 response. The secondary endpoints will include progression-free survival (PFS), overall survival, radiologic PFS, PSA response rate at 6 and 12 months.
- Conditions
- Prostate Cancer
- Being tested
- Nivolumab
- Keywords
- prostate cancer
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called BMS-936558
Nivolumab
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab | Experimental | All patients will receive Nivolumab 240 mg every 14 days until progression or unacceptable toxicity Receives: Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
PSA response rate
PSA partial response is defined as a ≥ 50% decline in PSA from cycle 1 day 1 (baseline) PSA value. This PSA decline must be confirmed as sustained by a second PSA value obtained ≥ 3 weeks later.
Measured: through study completion, an average of 1 year
Secondary outcomes (6)
Time to PSA progression
Measured: through study completion, an average of 1 year
PSA Response Rate at 6 and 12 months
Measured: through study completion, an average of 1 year
Radiological progression-free survival (rPFS)
Measured: through study completion, an average of 1 year
Time to Radiographic Progression
Measured: through study completion, an average of 1 year
Progression free survival (PFS)
Measured: through study completion, an average of 1 year
Overall survival
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2017 (estimated)
- Study start1 Jun 2018
- Primary completion1 Jan 2022 (estimated)
- Study completion1 Mar 2022 (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.
- 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
- Not applicable
- Intervention model
- Single group
- Model description
- This is a Phase II, two-stage, multi-center, single-arm, and open-label trial of Nivolumab (BMS-936558) in patients with mCRPC who have progressed to a taxane-based chemotherapy regimen previously.
- Masking
- None (open label)
- Enrolment
- 38 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Moinhos de Vento
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Pedro Isaacsson, MD, Principal investigator, Hospital Moinhos de Vento
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03040791
- Sponsor's protocol ID
- 64121317.4.1001.5330
- Acronym
- ImmunoProst
- Status last verified
- Aug 2021
- First submitted
- 27 Jan 2017
- Last updated
- 26 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nivolumab in Prostate Cancer With DNA Repair Defects (ImmunoProst Trial)
- ClinicalTrials.gov ID
- NCT03040791
- Acronym / sponsor ID
- ImmunoProst / 64121317.4.1001.5330
- Conditions
- Prostate Cancer
- Keywords
- prostate cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 38 participants (estimated)
- Lead sponsor
- Hospital Moinhos de VentoUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 1 Jun 2018 (actual)
- Primary completion
- 1 Jan 2022 (estimated)
- Study completion
- 1 Mar 2022 (estimated)
- First posted
- 2 Feb 2017 (estimated)
- 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.
Prostate Cancer (PC) is the most frequent cancer in men, accounting for 21% of new cases of cancer in men in the United States. Among the four most incident tumors (breast, lung and colorectal cancer); prostate cancer is the only that does not have any predictive biomarker to guide the treatment. Even though the molecular heterogeneity of PC is well-documented, treatment has not been molecularly stratified and the need for genetic prognostic and predictive markers is critical.
DNA repair defects (DRD), mainly in the Homologous Recombination (HR) pathway (such as BRCA1, BRCA2, ATM and CHEK2) are emerging as potential biomarkers in prostate cancer. It is well known BRCA1 and BRCA2 carriers have better Progression-Free Survival (PFS) and Overall Survival (OS) than non-carriers in ovarian cancer. Differently than ovarian tumors that BRCA mutations provides a good prognosis, PC patients who harbor HR defects have a higher Gleason score 6, an increased risk of recurrence and poor prognosis. The predictive role of DRD in PC was demonstrated in a recent trial using Olaparib, a PARP inhibitor, in DRD carriers. This trial showed 88% of response rate with Olaparib, a PARP inhibitor that acts in HR pathway by synthetic lethality.
Recent data demonstrated important association between HR deficient high-grade serous ovarian cancer (HGSOC), high neoantigen load and high expression of PD-1/PD-L1 compared with HR proficient HGSOCs 10. This study showed that BRCA1 and BRCA2 mutations increase the number of tumor-infiltrating lymphocytes (TILs) and confer a better prognosis. The unprecedented success of immunotherapy in malignant disorders has provided evidence that the patient's immune system can be improved to attack established tumors, mainly melanoma, non-small cell lung cancer and kidney cancer. A high mutational burden increases the likelihood of the development of specific neoepitopes that would confer clinical benefit from CTLA-4 and PD-1 blockade.
These data showed that specific DNA repair defects increase the mutational burden, the expression of PD-1/PD-L1 and TILs; and could improve the response to immunotherapy in cancer. This rationale was already tested in a trial that evaluated the PD-1 checkpoint inhibitor Pembrolizumab in mismatch-repair deficient patients, a kind of DNA repair defect by definition. This important trial showed that this DRD predicted clinical benefit of immune checkpoint blockade in many types of cancer, especially colorectal cancer.
Detailed description
This is a Phase II, two-stage, multi-center, single-arm, and open-label trial of Nivolumab (BMS-936558) in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed to a taxane-based chemotherapy regimen previously. Eligible patients must have ECOG 0-2 and material for biomarker analysis. Prior enzalutamide, abiraterone and cabazitaxel are permitted but not necessary to enrollment. The germline and somatic DRD (BRCA1, BRCA2, ATM, PTEN, CHEK2, RAD51C, RAD51D, PALB2, MLH1, MSH2, MSH6, PMS2.) will be assessed by T-NGS of metastatic sites or by liquid biopsy. The primary endpoint is PSA 50 response rate (PSA50, following the Prostate Cancer Working Group 3 criteria). The trial will meet its endpoint if ≥ 3/29 men achieve a PSA50 response. The secondary endpoints will include progression-free survival (PFS), overall survival, radiologic PFS, PSA response rate at 6 and 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a Phase II, two-stage, multi-center, single-arm, and open-label trial of Nivolumab (BMS-936558) in patients with mCRPC who have progressed to a taxane-based chemotherapy regimen previously.
| Arm | Type | Receives |
|---|---|---|
| Nivolumab | Experimental | Drug: NivolumabAll patients will receive Nivolumab 240 mg every 14 days until progression or unacceptable toxicity |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Histologically confirmed adenocarcinoma of the prostate with tumor tissue available for molecular analyses. If archival tissue for biomarker analysis is not available then the patient must be willing to have a further biopsy to obtain tumor tissue for histological diagnosis.
- Metastatic Castrate-resistant prostate cancer (mCRPC), defined by:
- Documented prostate cancer progression, during treatment with Docetaxel, as assessed by the investigator with one of the following:
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 Appendix A: Performance Status Criteria
- Life expectancy > 24 weeks.
Key exclusion criteria (8 listed)
- Patients with any active known or suspected autoimmune disease. Patients with vitiligo, type I diabetes mellitus, controlled autoimmune hypothyroidism, psoriasis not requiring systemic treatment, or other conditions under control are permitted to enroll.
- Patients with conditions that needs systemic corticosteroids dose > Prednisolone 10 mg/day (or equivalent) or other immunosuppressive medications within 28 days prior to the first dose of study drug. Inhaled steroids are permitted if necessary.
- Patients with any known active chronic liver disease.
- Patients who have prior history of malignancy treated with curative intention in the past 2 years with the exception of basal cell carcinoma and squamous cell carcinoma of the skin, which were allowed in any case. Patients with other malignancies that do not fulfill the prior criteria could be considered for recruitment if they do not represent a competitive cause of death and have a low potential to progress to metastatic progression. Patients in this condition may be enrolled in the trial if approved after review by principal investigator.
- Known history of testing positive for human immunodeficiency virus (HIV), known acquired immunodeficiency syndrome (AIDS), or any positive test for hepatitis B or hepatitis C virus representing acute or chronic 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 |
|---|---|---|
| NivolumabAlso: BMS-936558Nivolumab | Drug | Nivolumab |
Primary outcome
PSA response rate
Time frame: through study completion, an average of 1 year
PSA partial response is defined as a ≥ 50% decline in PSA from cycle 1 day 1 (baseline) PSA value. This PSA decline must be confirmed as sustained by a second PSA value obtained ≥ 3 weeks later.
6 secondary outcomes
Time to PSA progression
Time frame: through study completion, an average of 1 year
PSA Response Rate at 6 and 12 months
Time frame: through study completion, an average of 1 year
Radiological progression-free survival (rPFS)
Time frame: through study completion, an average of 1 year
Time to Radiographic Progression
Time frame: through study completion, an average of 1 year
Progression free survival (PFS)
Time frame: through study completion, an average of 1 year
Overall survival
Time frame: through study completion, an average of 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2021.
- Individual participant dataSharing planned: Yes
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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.
Pedro Isaacsson, MD principal investigator
Hospital Moinhos de Vento
2 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 in people with Prostate Cancer, run by Hospital Moinhos de Vento at 2 sites in Brazil.
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 26 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 26 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Brazil. 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?
Results are not available in the source record.
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?
PSA response rate (time frame: through study completion, an average of 1 year). 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 26 Aug 2021.