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

Status unconfirmed · Phase 2

Conditions studied: Prostate Cancer, Prostate Cancer Metastatic

In brief

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.

Key facts

Study ID

NCT04116775

Run by

Julie Graff, MD

People needed

32

Starts

2019-10-30

Expected to finish

2023-10-01

Last updated by the study team

2022-06-23

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: not accepted.

You may qualify if…

• 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)

You may not qualify if…

• 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)

Where it is running

• VA Portland Health Care System — Portland, Oregon, United States (enrolling)

Full record on ClinicalTrials.gov

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