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CompletedNCT02489357Updated Nov 12, 2021Results posted

Pembrolizumab and Cryosurgery in Treating Patients With Newly Diagnosed, Oligo-metastatic Prostate Cancer

An interventional study of Cryosurgery and Degarelix in Stage IV Prostate Cancer, sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. Completed at 1 site in United States. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-11-12.

Sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
12
Allocation
Not applicable
Ages
18 Years and older
Sex
Male
01

Study 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). 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:

I. 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:

I. 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.

02

Conditions studied

  • Stage IV Prostate Cancer

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03

In context

Prostatic Neoplasms

6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,397 are open to participants now.

This study's enrollment of 12 is below the median of 58 across 4,821 interventional studies indexed under Prostatic Neoplasms.

Browse Prostatic Neoplasms studies →

Lead sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins is the lead sponsor of 572 studies on the registry; 73 are open to participants now.

Of its 111 completed or terminated interventional studies of FDA-regulated products, 67 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years and older
Sexes eligible
Male
Accepts healthy volunteers
No

Inclusion criteria

  • 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
  • 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

Exclusion criteria

Exclusion Criteria:

  • 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
  • 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)
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
12 participants (actual)

Study arms

  • Experimental
    Treatment (pembrolizumab, cryosurgery)

    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.

    Procedure: Cryosurgery · Drug: Degarelix · Other: Laboratory Biomarker Analysis · Biological: Pembrolizumab

Interventions

  • ProcedureCryosurgery

    Undergo whole gland cryoablation

    Also known as: CRYOABLATION, cryosurgical ablation

  • DrugDegarelix

    Given SC

    Also known as: FE200486, Firmagon

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • BiologicalPembrolizumab

    Given IV

    Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

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What researchers measure

Primary outcomes

  1. Number of Participants With PSA < 0.6 ng/mL

    Time frame: At 1 year

Other outcomes

  1. Expression of PD-1

    Number of participants with PD-1 expression in tumor tissue.

    Time frame: Baseline

  2. Expression of PD-L1

    Number of participants with PD-L1 expression in tumor tissue.

    Time frame: Baseline

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Results

Posted Apr 3, 2019

Participant flow

Participant flow — Overall Study
MilestoneTreatment (Pembrolizumab, Cryosurgery)
Started12
Completed12
Not completed0

Outcome measures

PrimaryNumber of Participants With PSA < 0.6 ng/mL
Time frame:
At 1 year
Reported as:
Count of participants · Participants
Number of Participants With PSA < 0.6 ng/mL
ParticipantsTreatment (Pembrolizumab, Cryosurgery)
Number of Participants With PSA < 0.6 ng/mL5
Other pre-specifiedExpression of PD-1

Number of participants with PD-1 expression in tumor tissue.

Time frame:
Baseline
Reported as:
Count of participants · Participants
Expression of PD-1
ParticipantsTreatment (Pembrolizumab, Cryosurgery)
Expression of PD-11
Other pre-specifiedExpression of PD-L1

Number of participants with PD-L1 expression in tumor tissue.

Time frame:
Baseline
Reported as:
Count of participants · Participants
Expression of PD-L1
ParticipantsTreatment (Pembrolizumab, Cryosurgery)
Expression of PD-L10

Adverse events

Collected over up to 2 years. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment (Pembrolizumab, Cryosurgery)0/12 (0%)0/12 (0%)12/12 (100%)
Most frequent other events
Showing 10 of 33
Most frequent other events
EventTreatment (Pembrolizumab, Cryosurgery)
FatigueGeneral disorders8/12
Hot flashesVascular disorders6/12
PainMusculoskeletal and connective tissue disorders4/12
EdemaBlood and lymphatic system disorders3/12
Urinary urgencyRenal and urinary disorders3/12
Urinary frequencyRenal and urinary disorders3/12
Injection site reactionGeneral disorders3/12
Groin PainGastrointestinal disorders3/12
Urinary incontinenceRenal and urinary disorders2/12
DepressionPsychiatric disorders2/12

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Treatment (Pembrolizumab, Cryosurgery)
<=18 years0
Between 18 and 65 years6
>=65 years6
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (Pembrolizumab, Cryosurgery)
Female0
Male12
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)Treatment (Pembrolizumab, Cryosurgery)
Region of Enrollment
Region of Enrollment(Participants)Treatment (Pembrolizumab, Cryosurgery)
United States12
08

Study locations

1 site
  • Johns Hopkins University/Sidney Kimmel Cancer Center
    Baltimore, Maryland 21287, United States
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References and documents

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 documents

  • Protocol and statistical analysis plan · Feb 2, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 12, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT02489357
Lead sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Jul 3, 2015
Start date
Dec 11, 2015
Primary completion
Nov 30, 2017
Completion
Nov 30, 2017
Results posted
Apr 3, 2019
Last update
Nov 12, 2021

Study contacts

Emmanuel Antonarakis, MD
principal investigator · Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Nov 2021. You cannot join it, but the record below documents what was studied.

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