Stage IV Prostate CancerNCT02489357
Pembrolizumab and Cryosurgery in Treating Patients With Newly Diagnosed, Oligo-metastatic Prostate Cancer
A study testing Cryosurgery, Degarelix and Laboratory Biomarker Analysis in people with Stage IV Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
This pilot phase II trial studies the side effects and how well pembrolizumab and cryosurgery work with short term androgen ablation to treat patients with prostate cancer that has traveled from the original tumor, through the body, and formed a small number of new tumors in other parts of the body (oligo-metastatic). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Stage IV Prostate Cancer
- What is being tested?
- Cryosurgery, Degarelix and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Dec 2015to 30 Nov 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 histologically or cytologically diagnosed oligo-metastatic prostate cancer; oligo-metastatic disease is defined to reflect men with low volume disease; specifically, oligo-metastatic disease is defined as less than 5 extra-pelvic metastases; metastatic lesions may be lymph nodes
- Be willing and able to provide written informed consent/assent for the trial
- Have available tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion
- Eastern Cooperative Oncology Group (ECOG) performance scale status of 0 or 1
- Demonstrate adequate organ function, all screening labs should be performed within 14 days of treatment initiation
- Absolute neutrophil count (ANC) >= 1,500/mcL
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- Platelets >= 100,000/mcL
- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L
- Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) =< 1.5 X upper limit of normal (ULN) OR >= 60 mL/min for subject with creatinine levels > 1.5 X institutional upper limit of normal (ULN)
- Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulant
- Have testosterone greater than 50 ng/dl
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
Who cannot join
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent; Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study; Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
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- Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis
- Has an active infection requiring systemic therapy
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Is expecting to father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
- Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis c (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] (qualitative) is detected)
- Has received a live vaccine within 30 days prior to the first dose of trial treatment
- Has severe voiding symptoms (International Prognostic Scoring System [IPSS] > 20) or urinary retention requiring a catheter
- Has contraindications to cryotherapy of the prostate, including: previous transurethral prostatic resection (TURP) with persistent transurethral resection (TUR) defect, existing peri-anal or recto-urethral fistula, previous external beam radiation therapy or brachytherapy, coagulopathy, inability to tolerate anesthesia (spinal or general), inability to tolerate transrectal ultrasound (i.e. history of previous abdominal perineal resection)
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
About this study
Official title: A Pilot Study of MK-3475 With Cryotherapy for Men With Newly Diagnosed Oligo-metastatic Prostate Cancer
This pilot phase II trial studies the side effects and how well pembrolizumab and cryosurgery work with short term androgen ablation to treat patients with prostate cancer that has traveled from the original tumor, through the body, and formed a small number of new tumors in other parts of the body (oligo-metastatic). Cryosurgery, also known as cryoablation or cryotherapy, kills tumor cells by freezing them. The process also incites an immune response within the ablated tumor. Giving monoclonal antibodies such as pembrolizumab which enhance a systemic anti-cancer immune response, may augment the effects of cryosurgery and increase tumor killing at distant (metastatic) sites.
Read the detailed description
PRIMARY OBJECTIVES:
- Assess feasibility via the proportion of men reaching a low prostate-specific antigen (PSA) nadir (< 0.6 ng/ml) at 1 year.
II. Evaluate the safety of cryotherapy to the prostate combined with pembrolizumab.
TERTIARY OBJECTIVES:
- To evaluate the effects of combination cryotherapy / pembrolizumab on programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) expression in the prostate as assessed by biopsy performed 6 months post treatment.
OUTLINE:
Patients receive standard of care androgen ablation with degarelix subcutaneously (SC) once a month for 8 months. Within 1 month of receiving degarelix, patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Within 3 days of receiving the first dose of pembrolizumab, patients undergo whole gland cryoablation of the prostate.
After completion of study treatment, patients are followed up at 30 days and then every 12 weeks for up to 1 year.
- Conditions
- Stage IV Prostate Cancer
- Being tested
- Cryosurgery, Degarelix, Laboratory Biomarker Analysis, Pembrolizumab
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CryosurgeryProcedure or surgery
Also called CRYOABLATION, cryosurgical ablation
Undergo whole gland cryoablation
DegarelixDrug
Also called FE200486, Firmagon
Given SC
Laboratory Biomarker AnalysisOther
Correlative studies
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (pembrolizumab, cryosurgery) | Experimental | Patients receive standard of care degarelix SC once a month for 8 months. Within 1 month of receiving degarelix, patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Within 3 days of receiving pembrolizumab, patients undergo whole gland cryoablation of the prostate. Receives: Procedure: Cryosurgery; Drug: Degarelix; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With PSA < 0.6 ng/mL
Measured: At 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2015 (estimated)
- Study start11 Dec 2015
- Primary completion30 Nov 2017
- Study completion30 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Stage IV Prostate CancerStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Emmanuel Antonarakis, MD, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02489357
- Sponsor's protocol ID
- J1534
- Other IDs
- NCI-2015-00981, IRB00045444, MK-3475, P30CA006973
- Status last verified
- Nov 2021
- First submitted
- 30 Jun 2015
- Last updated
- 12 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Ross AE, Hurley PJ, Tran PT, Rowe SP, Benzon B, Neal TO, Chapman C, Harb R, Milman Y, Trock BJ, Drake CG, Antonarakis ES. A pilot trial of pembrolizumab plus prostatic cryotherapy for men with newly diagnosed oligometastatic hormone-sensitive prostate cancer. Prostate Cancer Prostatic Dis. 2020 Mar;23(1):184-193. doi: 10.1038/s41391-019-0176-8. Epub 2019 Oct 14.
PubMed 31611635
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of MK-3475 With Cryotherapy for Men With Newly Diagnosed Oligo-metastatic Prostate Cancer
- ClinicalTrials.gov ID
- NCT02489357
- Acronym / sponsor ID
- J1534
- Conditions
- Stage IV Prostate Cancer
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 11 Dec 2015 (actual)
- Primary completion
- 30 Nov 2017 (actual)
- Study completion
- 30 Nov 2017 (actual)
- First posted
- 3 Jul 2015 (estimated)
- Results
- Posted 3 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot phase II trial studies the side effects and how well pembrolizumab and cryosurgery work with short term androgen ablation to treat patients with prostate cancer that has traveled from the original tumor, through the body, and formed a small number of new tumors in other parts of the body (oligo-metastatic). Cryosurgery, also known as cryoablation or cryotherapy, kills tumor cells by freezing them. The process also incites an immune response within the ablated tumor. Giving monoclonal antibodies such as pembrolizumab which enhance a systemic anti-cancer immune response, may augment the effects of cryosurgery and increase tumor killing at distant (metastatic) sites.
Detailed description
PRIMARY OBJECTIVES:
- Assess feasibility via the proportion of men reaching a low prostate-specific antigen (PSA) nadir (< 0.6 ng/ml) at 1 year.
II. Evaluate the safety of cryotherapy to the prostate combined with pembrolizumab.
TERTIARY OBJECTIVES:
- To evaluate the effects of combination cryotherapy / pembrolizumab on programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) expression in the prostate as assessed by biopsy performed 6 months post treatment.
OUTLINE:
Patients receive standard of care androgen ablation with degarelix subcutaneously (SC) once a month for 8 months. Within 1 month of receiving degarelix, patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Within 3 days of receiving the first dose of pembrolizumab, patients undergo whole gland cryoablation of the prostate.
After completion of study treatment, patients are followed up at 30 days and then every 12 weeks for up to 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (pembrolizumab, cryosurgery) | Experimental | Procedure: Cryosurgery, Drug: Degarelix, Other: Laboratory Biomarker Analysis, Biological: PembrolizumabPatients receive standard of care degarelix SC once a month for 8 months. Within 1 month of receiving degarelix, patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Within 3 days of receiving pembrolizumab, patients undergo whole gland cryoablation of the prostate. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Have histologically or cytologically diagnosed oligo-metastatic prostate cancer; oligo-metastatic disease is defined to reflect men with low volume disease; specifically, oligo-metastatic disease is defined as less than 5 extra-pelvic metastases; metastatic lesions may be lymph nodes
- Be willing and able to provide written informed consent/assent for the trial
- Have available tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion
- Eastern Cooperative Oncology Group (ECOG) performance scale status of 0 or 1
- Demonstrate adequate organ function, all screening labs should be performed within 14 days of treatment initiation
Key exclusion criteria (18 listed)
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent; Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study; Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
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 |
|---|---|---|
| CryosurgeryAlso: CRYOABLATION, cryosurgical ablationUndergo whole gland cryoablation | Procedure or surgery | Treatment (pembrolizumab, cryosurgery) |
| DegarelixAlso: FE200486, FirmagonGiven SC | Drug | Treatment (pembrolizumab, cryosurgery) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (pembrolizumab, cryosurgery) |
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given IV | Biological | Treatment (pembrolizumab, cryosurgery) |
Primary outcome
Number of Participants With PSA < 0.6 ng/mL
Time frame: At 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 31611635Ross AE, Hurley PJ, Tran PT, Rowe SP, Benzon B, Neal TO, Chapman C, Harb R, Milman Y, Trock BJ, Drake CG, Antonarakis ES. A pilot trial of pembrolizumab plus prostatic cryotherapy for men with newly diagnosed oligometastatic hormone-sensitive prostate cancer. Prostate Cancer Prostatic Dis. 2020 Mar;23(1):184-193. doi: 10.1038/s41391-019-0176-8. Epub 2019 Oct 14.
- 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.
Emmanuel Antonarakis, MD principal investigator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cryosurgery, Degarelix and Laboratory Biomarker Analysis in people with Stage IV Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
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 15 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 12 Nov 2021. 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 States. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With PSA < 0.6 ng/mL (time frame: At 1 year). 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 NCT02489357, which also lists 1 linked publication.
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 12 Nov 2021.