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

NCT02489357 | Completed Results DMC

• 5 other identifiers: J1534NCI-2015-00981IRB00045444MK-3475P30CA006973
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Stage IV Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With PSA < 0.6 ng/mL

  At 1 year

Other Outcomes (2)

• Expression of PD-1

  Baseline

• Expression of PD-L1

  Baseline

Study Arms (1)

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.

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

Interventions

Cryosurgery PROCEDURE

Undergo whole gland cryoablation

Also known as: CRYOABLATION, cryosurgical ablation

Treatment (pembrolizumab, cryosurgery)

Degarelix DRUG

Given SC

Also known as: FE200486, Firmagon

Treatment (pembrolizumab, cryosurgery)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, cryosurgery)

Pembrolizumab BIOLOGICAL

Given IV

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

Treatment (pembrolizumab, cryosurgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Related Publications (1)

• 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.

  PMID: 31611635 RESULT

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Cryosurgery; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; pembrolizumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Ablation Techniques; Surgical Procedures, Operative

Results Point of Contact

• Title: Emmanuel Antonarakis, MD
• Organization: Johns Hopkins University/Sidney Kimmel Cancer Center

eantona1@jhmi.edu

410-502-7528

Study Officials

• Emmanuel Antonarakis, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2015
• First Posted: July 3, 2015
• Study Start: December 11, 2015
• Primary Completion: November 30, 2017
• Study Completion: November 30, 2017
• Last Updated: November 12, 2021
• Results First Posted: April 3, 2019

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)