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

  • End date
    Oct 23, 2023
  • participants needed
  • sponsor
    Julie Graff, MD
Updated on 17 February 2022
platelet count
measurable disease
growth factor
gilbert's syndrome
neutrophil count
liver metastasis
antiandrogen therapy
bone disease
bone metastases
adenocarcinoma of prostate


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.



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.


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.

Condition Prostate Cancer, Prostate Cancer Metastatic
Treatment Pembrolizumab, Enzalutamide, fecal microbiota transplant
Clinical Study IdentifierNCT04116775
SponsorJulie Graff, MD
Last Modified on17 February 2022


Yes No Not Sure

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 unambigulously indicative of advanced adenocarcinoma
Receive care through a Veterans Affairs Hospital
Have metastatic castration resistant prostate cancer with castrate-level testosterone (<50 ng/dL)
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
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 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 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
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

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)
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, idiopathic chronic constipation, or chronic diarrhea, 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
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
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