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

NCT04116775 | Unknown Phase 2 FDA Drug

• 2 other identifiers: MISP 58002MIRB 4395
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer; Prostate Cancer Metastatic

Keywords

Microbiota; Prostate; Metastatic; Programmed cell death protein 1; Pembrolizumab; Prostatic Neoplasms

Outcome Measures

Primary Outcomes (1)

• 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.

  From 14 weeks up to 2 years

Secondary Outcomes (9)

• Percent PSA change

  From 12 weeks up to 2 years

• Radiographic response rate

  2.5 years

• Time to PSA progression

  2 years

• Time to radiographic progression

  2.5 years

• PSA progression-free survival

  2 years

Study Arms (1)

Treatment

EXPERIMENTAL

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.

Biological: Fecal microbiota transplant; Drug: Pembrolizumab; Drug: Enzalutamide

Interventions

Fecal microbiota transplant BIOLOGICAL

A total of 100 mL of a mixture of stool and saline will be transplanted via endoscopy once.

Also known as: FMT, Fecal transplant

Treatment

Pembrolizumab DRUG

Pembrolizumab 200 mg administered as a 30 minute infusion every 3 weeks.

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

Treatment

Enzalutamide DRUG

Daily oral dose.

Also known as: Xtandi, MDV3100, ASP9785

Treatment

Eligibility Criteria

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

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.

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.

Sponsors & Collaborators

• Julie Graff, MD: lead
• Merck Sharp & Dohme LLC: collaborator
• Prostate Cancer Foundation: collaborator
• Johns Hopkins University: collaborator
• Oregon Health and Science University: collaborator

Study Sites (1)

VA Portland Health Care System

Portland, Oregon, 97239, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Interventions

Fecal Microbiota Transplantation; pembrolizumab; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Julie N Graff, MD

  Portland VA Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carmen Iben

CONTACT

(503) 220-8262; iben@ohsu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Section Chief-Hematology and Oncology

Model Details: 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.

Study Record Dates

• First Submitted: October 3, 2019
• First Posted: October 7, 2019
• Study Start: October 30, 2019
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: June 23, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)