search
Back to results

Fecal Microbiota Transplant and Pembrolizumab for Men With Metastatic Castration Resistant Prostate Cancer.

Primary Purpose

Prostate Cancer, Prostate Cancer Metastatic

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fecal microbiota transplant
Pembrolizumab
Enzalutamide
Sponsored by
Julie Graff, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring Microbiota, Prostate, Metastatic, Programmed cell death protein 1, Pembrolizumab, Prostatic Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Be willing and able to provide written informed consent/assent for the trial prior to the performance of any protocol-related procedures that are not part of normal care.
  2. Be ≥ 18 years of age at the time the informed consent is signed.
  3. Histologically or cytologically documented adenocarcinoma of the prostate. Patients without histologically confirmed adenocarcinoma may be eligible if both the treating physician and the study PI agree that the patient's history is unambiguously indicative of advanced adenocarcinoma.
  4. Receive care through a Veterans Affairs Hospital or is eligible for care at VHA.
  5. Have metastatic castration resistant prostate cancer with castrate-level testosterone (<50 ng/dL).

    a. Participants must maintain a castrate-level testosterone during the study.

  6. Have disease progression defined by one or more of the following three criteria:

    1. PSA > 2.0 ng/mL at time of screening and rising PSA by at least 2 consecutive measurements a minimum of 1-week apart.
    2. Soft tissue progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
    3. Bone disease progression as defined by the PCWG3.
  7. Have measurable disease based on RECIST v.1.1 modified as described by the PCWG3 or non-measurable disease with bone metastases.

    a. Participants with measurable disease must have at least one lesion that is ≥10 mm in longest diameter for a soft tissue lesion, or ≥15 mm in short axis for a lymph node.

  8. Have a metastatic lesion that can be safely biopsied and be willing to undergo the tumor biopsy. If the participant is on anticoagulation, it must be safe to hold the anticoagulation for the biopsy.
  9. Have had a PSA response to enzalutamide (defined as a PSA decline of 50% or more), but now showing signs of PSA and/or radiographic progression per PCWG3 and/or RECIST 1.1. (Patients must be continuously on enzalutamide prior to joining the main study. They may not have had progression on enzalutamide and then challenge with new therapy and then restarted on enzalutamide.)
  10. Participants must discontinue antiandrogen therapy (ie, bicalutamide, flutamide, nilutamide) at least 4-6 weeks prior to registration with no evidence of PSA decline after washout.

    1. Bicalutamide: Washout period at least 6 weeks
    2. Flutamide and nilutamide: Washout period at least 4 weeks
  11. Participants must discontinue therapies for mCRPC, with the exception of enzalutamide and a GnRH agent, for 5 half-lives or 28 days, whichever is shorter.

    1. Prior treatment with sipuleucel-T, radium-223, or abiraterone is allowed.
    2. Tissue biopsy may be performed during washout period.
  12. Have a performance status of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
  13. Demonstrate adequate organ function on screening laboratory tests performed within 14 days of treatment initiation and as evidenced by:

    1. Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within ≤ 7 days of assessment)
    2. WBC > 2,000/mm3 without growth factor support (within ≤ 7 days days of assessment)
    3. Absolute neutrophil count ≥ 1,500/mm3 without growth factor support or transfusion (within < 28 days of assessment)
    4. Platelet count ≥ 100,000/mm3
    5. Serum creatinine < 1.5 x upper limit of normal (ULN) or measured or calculated (calculated per institutional standard) creatinine clearance ≥ 60 mL/min for participant with creatinine levels > 1.5 x institutional ULN. GFR can also be used in place of creatinine or CrCl.
    6. Serum total bilirubin < 1.5 x ULN or ≤ 2.0 x ULN for participants with liver metastases

      • Participants with Gilbert's syndrome must have ≤ 3 x ULN and no liver lesions
    7. Aspartate transaminase (AST) (SGOT) and alanine transaminase (ALT) (SGPT) ≤ 2.5 x ULN or ≤ 5.0 x ULN for participants with liver metastases.
    8. Albumin ≥ 2.5 mg/dL.
    9. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy, as long as PT is within therapeutic range of intended use of anticoagulants.
    10. Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy, as long as PTT is within therapeutic range of intended use of anticoagulants.
  14. Male participants of reproductive potential must agree to use an adequate method of contraception, starting with the first dose of study intervention and through 120 days after the last dose of study therapy. Contraception is not required if the patient's partner is a woman who is post-menopausal. Subjects of reproductive potential must agree to avoid impregnating a partner by complying with one of the following:

    Practice abstinence from heterosexual activity; abstinence (relative to heterosexual activity) can be used as the sole method of contraception if it is consistently employed as the subject's preferred and usual lifestyle. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception.

    OR

    Have their partner use acceptable contraception during heterosexual activity. Acceptable methods of contraception are:

    Single method (one of the following is acceptable):

    • Intrauterine device (IUD)
    • Contraceptive rod implanted into the skin.

    Combination method (requires use of two of the following):

    • Diaphragm with spermicide (cannot be used in conjunction with cervical cap/spermicide)
    • Cervical cap with spermicide (nulliparous women only)
    • Contraceptive sponge (nulliparous women only)
    • Male condom or female condom (cannot be used together)
    • Hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or progestin-only pill), contraceptive skin patch, vaginal contraceptive ring, or subcutaneous contraceptive injection.
  15. Participants must be able and willing to comply with the study visit schedule and study procedures.

Exclusion Criteria:

  1. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy. Superficial bladder cancer is also permitted provided it is monitored and treated locally.
  2. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study intervention 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 study intervention. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
  3. Uncontrolled disease-related bone pain or other symptoms that suggest the participant should imminently go onto chemotherapy.
  4. Those with tumors having known microsatellite instability will be excluded. Participants found to have microsatellite instability in their tumors after analysis of the on-study biopsy will not be eligible to serve as FMT donors, but will be permitted on the study.
  5. Prior taxane-based chemotherapy (in any setting- castration sensitive or resistant).
  6. Has had prior therapy with an anti-CTLA4, anti-PD-1 or anti-PD-L1 antibody.
  7. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of study treatment or who has not recovered (ie, ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  8. Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  9. Has had prior targeted small molecule therapy within 2 weeks prior to the first dose of study treatment or who has not recovered (ie, ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.

    1. Note: Participants with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
    2. Note: If a participant received major surgery, he must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  10. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  11. Has received broad-spectrum antibiotics within 3 months of first dose of pembrolizumab.
  12. Has a history of seizure, unless he had a mass in his brain that has been removed, such as a meningioma.
  13. Has a diagnosis of immunodeficiency or conditions that need systemic corticosteroid replacement therapy > 10 mg/day prednisone (or equivalent) or other immunosuppressive medications within 28 days prior to the first dose of study intervention. Inhaled steroids are permitted if necessary.
  14. Has any active known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, controlled autoimmune hypothyroidism, psoriasis not requiring systemic treatment, or other conditions under control are permitted to enroll. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy < 10 mg of prednisone/day for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  15. Has a known history of active TB (Bacillus Tuberculosis).
  16. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis .
  17. Has an active infection requiring systemic therapy.
  18. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  19. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  20. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients Testing positive for any of the following infectious diseases (criteria 21-22).
  21. Evidence of the following infectious agents:

    1. Stool pathogens: Clostridium difficilie toxin B by PCR, Giardia antigen, Cryptosporidium antigen, Acid-fast stan for Cyclospora or Isospora, Ova and parasites, Helicobacterial pylori antigen positivity, Salmonella spp., Shigella spp., Campylobacter spp., Shiga-toxin producing Escherichia coli, Methicillin Resistant Staphylococcus aureus, Vancomycin Resistant Enterococcus spp., Carbapenem Resistant Enterobacteriaceae, ESBL producing E. coli, Aeromonas spp., Plesiomonas spp., Yersinia spp., Vibrio spp., Entamoeba histolytica, Rotavirus, Adenovirus, Norovirus
    2. Blood pathogens: Positive for HIV, type 1 or 2; Hepatitis A IgM; Hepatitis B antigen, anti-HBC (both IgG and IgM), and anti-HBs; Hepatitis C antigen; T. pallidum antibody; FTA-ABS (if positive T. pallidum screen)
    3. COVID-19 (unless vaccinated against COVID-19)
  22. Risk factors for contracting an illness:

    1. Ongoing high-risk behaviors (e.g. men who have sex with men, men who have sex for money, men who use intravenous drugs)
    2. Tattoo or body piercing within 6 months
    3. Risk factors for Creutzfeldt-Jakob disease
    4. Travel within the past 6 months to areas of the world where diarrheal illnesses are endemic or risk of traveler's diarrhea is high
  23. Known current communicable disease (e.g. upper respiratory infection).
  24. Gastrointestinal co-morbidities: history of inflammatory bowel disease, history of irritable bowel syndrome or idiopathic chronic constipation, history of chronic diarrhea related to inflammatory bowel disease with current diarrheal symptoms, history of gastrointestinal malignancy or known polyposis.
  25. Major immunosuppressive medications, e.g., calcineurin inhibitors, exogenous glucocorticoids, biologic agents, etc.
  26. Systemic antineoplastic agents other than enzalutamide and LHRH agonist or antagonist in the past 4 weeks.
  27. Has received a live vaccine within 30 days of planned start of study intervention. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (eg, Flu-Mist®) are live attenuated vaccines, and are not allowed.

Sites / Locations

  • VA Portland Health Care SystemRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

INITIAL TREATMENT PHASE: Patients progressing on enzalutamide will receive 200 mg of pembrolizumab IV over 30 minutes. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients continue to receive standard of care enzalutamide PO daily and androgen deprivation therapy. ASSESSMENT PHASE: After completion of the initial treatment phase, patients will have their disease assessed by tumor imaging. Patients who respond to treatment will become stool donors to patients who do not respond. Non-responders will move on to the retreatment phase. RETREATMENT PHASE: Non-responders will undergo a fecal transplant and be retreated with 200 mg of pembrolizumab IV over 30 minutes. Treatment repeats every 3 weeks for an additional 4 cycles in the absence of disease progression or unacceptable toxicity. Patients continue to receive standard of care enzalutamide PO daily and androgen deprivation therapy.

Outcomes

Primary Outcome Measures

Anticancer effect of fecal microbiota transplant from responders to pembrolizumab to non-responders.
Percentage of participants with a PSA decline of ≥ 50% at any time point on study after FMT.

Secondary Outcome Measures

Percent PSA change
Change between baseline PSA and nadir PSA, in a negative direction. If no decrease in PSA, change between baseline PSA and PSA at 12 weeks.
Radiographic response rate
Best response: Percentage of participants who have stable disease, partial response, complete response, and progressive disease.
Time to PSA progression
Time from first treatment with pembrolizumab to confirmed PSA progression per PCWG3.
Time to radiographic progression
Time from first treatment with pembrolizumab to radiographic progression per PCWG3 and RECIST 1.1.
PSA progression-free survival
Time from first treatment with pembrolizumab to confirmed PSA progression per PCWG3 or death.
Radiographic progression-free survival
Time from first treatment with pembrolizumab to radiographic progression per PCWG3 and RECIST 1.1 or death.
Overall survival
Time from first treatment with pembrolizumab to death.
Time to next therapy
Time from first treatment with pembrolizumab to day 1 of the next systemic prostate cancer therapy.
Characterization of safety profile
All adverse events and their relationships to study drugs and procedures will be recorded.

Full Information

First Posted
October 3, 2019
Last Updated
June 21, 2022
Sponsor
Julie Graff, MD
Collaborators
Merck Sharp & Dohme LLC, Prostate Cancer Foundation, Johns Hopkins University, Oregon Health and Science University
search

1. Study Identification

Unique Protocol Identification Number
NCT04116775
Brief Title
Fecal Microbiota Transplant and Pembrolizumab for Men With Metastatic Castration Resistant Prostate Cancer.
Official Title
A Phase II Single Arm Study of Fecal Microbiota Transplant (FMT) in Men With Metastatic Castration Resistant Prostate Cancer Whose Cancer Has Not Responded to Enzalutamide + Pembrolizumab
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 30, 2019 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
October 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Julie Graff, MD
Collaborators
Merck Sharp & Dohme LLC, Prostate Cancer Foundation, Johns Hopkins University, Oregon Health and Science University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
All patients will be required to have a biopsy of a metastatic tumor deposit at study entry. Pembrolizumab will be administered at a dose of 200 mg as a 30 minute IV infusion every 3 weeks. Enzalutamide will be continued at dose of 160 mg orally every day. Patients who have neither rapid disease progression or disease response will undergo a fecal microbiota transplant, have a second biopsy (if medically feasible), and be re-treated with pembrolizumab.
Detailed Description
PRIMARY OBJECTIVE: To determine the anticancer effect of fecal microbiota transplant from participants who respond to pembrolizumab into those who have not responded in metastatic castration resistant prostate cancer. OUTLINE: The investigators propose to study the effects of fecal microbiota transplant (FMT) in patients whose disease does not respond to treatment with the combination of pembrolizumab and enzalutamide. Patients will remain on enzalutamide throughout the study and be treated with pembrolizumab for 4 cycles. Their disease will be assessed by tumor imaging. Patients whose disease responds to treatment will become stool donors to non-responders. Non-responders will undergo a second biopsy (if medically feasible) and be re-treated with pembrolizumab.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer, Prostate Cancer Metastatic
Keywords
Microbiota, Prostate, Metastatic, Programmed cell death protein 1, Pembrolizumab, Prostatic Neoplasms

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Single arm, open-label phase II study of fecal microbiota transplant for metastatic castration-resistant prostate cancer that has not responded to treatment with pembrolizumab and enzalutamide.
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
INITIAL TREATMENT PHASE: Patients progressing on enzalutamide will receive 200 mg of pembrolizumab IV over 30 minutes. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients continue to receive standard of care enzalutamide PO daily and androgen deprivation therapy. ASSESSMENT PHASE: After completion of the initial treatment phase, patients will have their disease assessed by tumor imaging. Patients who respond to treatment will become stool donors to patients who do not respond. Non-responders will move on to the retreatment phase. RETREATMENT PHASE: Non-responders will undergo a fecal transplant and be retreated with 200 mg of pembrolizumab IV over 30 minutes. Treatment repeats every 3 weeks for an additional 4 cycles in the absence of disease progression or unacceptable toxicity. Patients continue to receive standard of care enzalutamide PO daily and androgen deprivation therapy.
Intervention Type
Biological
Intervention Name(s)
Fecal microbiota transplant
Other Intervention Name(s)
FMT, Fecal transplant
Intervention Description
A total of 100 mL of a mixture of stool and saline will be transplanted via endoscopy once.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda, Lambrolizumab, MK-3475, SCH 900475
Intervention Description
Pembrolizumab 200 mg administered as a 30 minute infusion every 3 weeks.
Intervention Type
Drug
Intervention Name(s)
Enzalutamide
Other Intervention Name(s)
Xtandi, MDV3100, ASP9785
Intervention Description
Daily oral dose.
Primary Outcome Measure Information:
Title
Anticancer effect of fecal microbiota transplant from responders to pembrolizumab to non-responders.
Description
Percentage of participants with a PSA decline of ≥ 50% at any time point on study after FMT.
Time Frame
From 14 weeks up to 2 years
Secondary Outcome Measure Information:
Title
Percent PSA change
Description
Change between baseline PSA and nadir PSA, in a negative direction. If no decrease in PSA, change between baseline PSA and PSA at 12 weeks.
Time Frame
From 12 weeks up to 2 years
Title
Radiographic response rate
Description
Best response: Percentage of participants who have stable disease, partial response, complete response, and progressive disease.
Time Frame
2.5 years
Title
Time to PSA progression
Description
Time from first treatment with pembrolizumab to confirmed PSA progression per PCWG3.
Time Frame
2 years
Title
Time to radiographic progression
Description
Time from first treatment with pembrolizumab to radiographic progression per PCWG3 and RECIST 1.1.
Time Frame
2.5 years
Title
PSA progression-free survival
Description
Time from first treatment with pembrolizumab to confirmed PSA progression per PCWG3 or death.
Time Frame
2 years
Title
Radiographic progression-free survival
Description
Time from first treatment with pembrolizumab to radiographic progression per PCWG3 and RECIST 1.1 or death.
Time Frame
2.5 years
Title
Overall survival
Description
Time from first treatment with pembrolizumab to death.
Time Frame
3 years
Title
Time to next therapy
Description
Time from first treatment with pembrolizumab to day 1 of the next systemic prostate cancer therapy.
Time Frame
2.5 years
Title
Characterization of safety profile
Description
All adverse events and their relationships to study drugs and procedures will be recorded.
Time Frame
2.5 years

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Be willing and able to provide written informed consent/assent for the trial prior to the performance of any protocol-related procedures that are not part of normal care. Be ≥ 18 years of age at the time the informed consent is signed. Histologically or cytologically documented adenocarcinoma of the prostate. Patients without histologically confirmed adenocarcinoma may be eligible if both the treating physician and the study PI agree that the patient's history is unambiguously indicative of advanced adenocarcinoma. Receive care through a Veterans Affairs Hospital or is eligible for care at VHA. Have metastatic castration resistant prostate cancer with castrate-level testosterone (<50 ng/dL). a. Participants must maintain a castrate-level testosterone during the study. Have disease progression defined by one or more of the following three criteria: PSA > 2.0 ng/mL at time of screening and rising PSA by at least 2 consecutive measurements a minimum of 1-week apart. Soft tissue progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Bone disease progression as defined by the PCWG3. Have measurable disease based on RECIST v.1.1 modified as described by the PCWG3 or non-measurable disease with bone metastases. a. Participants with measurable disease must have at least one lesion that is ≥10 mm in longest diameter for a soft tissue lesion, or ≥15 mm in short axis for a lymph node. Have a metastatic lesion that can be safely biopsied and be willing to undergo the tumor biopsy. If the participant is on anticoagulation, it must be safe to hold the anticoagulation for the biopsy. Have had a PSA response to enzalutamide (defined as a PSA decline of 50% or more), but now showing signs of PSA and/or radiographic progression per PCWG3 and/or RECIST 1.1. (Patients must be continuously on enzalutamide prior to joining the main study. They may not have had progression on enzalutamide and then challenge with new therapy and then restarted on enzalutamide.) Participants must discontinue antiandrogen therapy (ie, bicalutamide, flutamide, nilutamide) at least 4-6 weeks prior to registration with no evidence of PSA decline after washout. Bicalutamide: Washout period at least 6 weeks Flutamide and nilutamide: Washout period at least 4 weeks Participants must discontinue therapies for mCRPC, with the exception of enzalutamide and a GnRH agent, for 5 half-lives or 28 days, whichever is shorter. Prior treatment with sipuleucel-T, radium-223, or abiraterone is allowed. Tissue biopsy may be performed during washout period. Have a performance status of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale. Demonstrate adequate organ function on screening laboratory tests performed within 14 days of treatment initiation and as evidenced by: Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within ≤ 7 days of assessment) WBC > 2,000/mm3 without growth factor support (within ≤ 7 days days of assessment) Absolute neutrophil count ≥ 1,500/mm3 without growth factor support or transfusion (within < 28 days of assessment) Platelet count ≥ 100,000/mm3 Serum creatinine < 1.5 x upper limit of normal (ULN) or measured or calculated (calculated per institutional standard) creatinine clearance ≥ 60 mL/min for participant with creatinine levels > 1.5 x institutional ULN. GFR can also be used in place of creatinine or CrCl. Serum total bilirubin < 1.5 x ULN or ≤ 2.0 x ULN for participants with liver metastases Participants with Gilbert's syndrome must have ≤ 3 x ULN and no liver lesions Aspartate transaminase (AST) (SGOT) and alanine transaminase (ALT) (SGPT) ≤ 2.5 x ULN or ≤ 5.0 x ULN for participants with liver metastases. Albumin ≥ 2.5 mg/dL. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy, as long as PT is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy, as long as PTT is within therapeutic range of intended use of anticoagulants. Male participants of reproductive potential must agree to use an adequate method of contraception, starting with the first dose of study intervention and through 120 days after the last dose of study therapy. Contraception is not required if the patient's partner is a woman who is post-menopausal. Subjects of reproductive potential must agree to avoid impregnating a partner by complying with one of the following: Practice abstinence from heterosexual activity; abstinence (relative to heterosexual activity) can be used as the sole method of contraception if it is consistently employed as the subject's preferred and usual lifestyle. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception. OR Have their partner use acceptable contraception during heterosexual activity. Acceptable methods of contraception are: Single method (one of the following is acceptable): Intrauterine device (IUD) Contraceptive rod implanted into the skin. Combination method (requires use of two of the following): Diaphragm with spermicide (cannot be used in conjunction with cervical cap/spermicide) Cervical cap with spermicide (nulliparous women only) Contraceptive sponge (nulliparous women only) Male condom or female condom (cannot be used together) Hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or progestin-only pill), contraceptive skin patch, vaginal contraceptive ring, or subcutaneous contraceptive injection. Participants must be able and willing to comply with the study visit schedule and study procedures. Exclusion Criteria: Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy. Superficial bladder cancer is also permitted provided it is monitored and treated locally. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study intervention 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 study intervention. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability. Uncontrolled disease-related bone pain or other symptoms that suggest the participant should imminently go onto chemotherapy. Those with tumors having known microsatellite instability will be excluded. Participants found to have microsatellite instability in their tumors after analysis of the on-study biopsy will not be eligible to serve as FMT donors, but will be permitted on the study. Prior taxane-based chemotherapy (in any setting- castration sensitive or resistant). Has had prior therapy with an anti-CTLA4, anti-PD-1 or anti-PD-L1 antibody. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of study treatment or who has not recovered (ie, ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease. Has had prior targeted small molecule therapy within 2 weeks prior to the first dose of study treatment or who has not recovered (ie, ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Participants with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If a participant received major surgery, he must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. Has received broad-spectrum antibiotics within 3 months of first dose of pembrolizumab. Has a history of seizure, unless he had a mass in his brain that has been removed, such as a meningioma. Has a diagnosis of immunodeficiency or conditions that need systemic corticosteroid replacement therapy > 10 mg/day prednisone (or equivalent) or other immunosuppressive medications within 28 days prior to the first dose of study intervention. Inhaled steroids are permitted if necessary. Has any active known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, controlled autoimmune hypothyroidism, psoriasis not requiring systemic treatment, or other conditions under control are permitted to enroll. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy < 10 mg of prednisone/day for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Has a known history of active TB (Bacillus Tuberculosis). Has a history of (non-infectious) pneumonitis that required steroids or current 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 participant's participation for the full duration of the trial, or is not in the best interest of the participant 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. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients Testing positive for any of the following infectious diseases (criteria 21-22). Evidence of the following infectious agents: Stool pathogens: Clostridium difficilie toxin B by PCR, Giardia antigen, Cryptosporidium antigen, Acid-fast stan for Cyclospora or Isospora, Ova and parasites, Helicobacterial pylori antigen positivity, Salmonella spp., Shigella spp., Campylobacter spp., Shiga-toxin producing Escherichia coli, Methicillin Resistant Staphylococcus aureus, Vancomycin Resistant Enterococcus spp., Carbapenem Resistant Enterobacteriaceae, ESBL producing E. coli, Aeromonas spp., Plesiomonas spp., Yersinia spp., Vibrio spp., Entamoeba histolytica, Rotavirus, Adenovirus, Norovirus Blood pathogens: Positive for HIV, type 1 or 2; Hepatitis A IgM; Hepatitis B antigen, anti-HBC (both IgG and IgM), and anti-HBs; Hepatitis C antigen; T. pallidum antibody; FTA-ABS (if positive T. pallidum screen) COVID-19 (unless vaccinated against COVID-19) Risk factors for contracting an illness: Ongoing high-risk behaviors (e.g. men who have sex with men, men who have sex for money, men who use intravenous drugs) Tattoo or body piercing within 6 months Risk factors for Creutzfeldt-Jakob disease Travel within the past 6 months to areas of the world where diarrheal illnesses are endemic or risk of traveler's diarrhea is high Known current communicable disease (e.g. upper respiratory infection). Gastrointestinal co-morbidities: history of inflammatory bowel disease, history of irritable bowel syndrome or idiopathic chronic constipation, history of chronic diarrhea related to inflammatory bowel disease with current diarrheal symptoms, history of gastrointestinal malignancy or known polyposis. Major immunosuppressive medications, e.g., calcineurin inhibitors, exogenous glucocorticoids, biologic agents, etc. Systemic antineoplastic agents other than enzalutamide and LHRH agonist or antagonist in the past 4 weeks. Has received a live vaccine within 30 days of planned start of study intervention. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (eg, Flu-Mist®) are live attenuated vaccines, and are not allowed.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Carmen Iben
Phone
(503) 220-8262
Ext
59502
Email
iben@ohsu.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julie N Graff, MD
Organizational Affiliation
Portland VA Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Portland Health Care System
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carmen Iben
Phone
503-220-8262
Ext
59502
Email
iben@ohsu.edu
First Name & Middle Initial & Last Name & Degree
Julie N Graff, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Fecal Microbiota Transplant and Pembrolizumab for Men With Metastatic Castration Resistant Prostate Cancer.

We'll reach out to this number within 24 hrs