Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Death

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Androgens

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

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

Fecal microbiota transplant

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

Enzalutamide

Carmen Iben

Julie N Graff, MD

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.

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.

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.

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

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

Percentage of participants with a PSA decline of ≥ 50% at any time point on study after FMT.

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.

Best response: Percentage of participants who have stable disease, partial response, complete response, and progressive disease.

Time from first treatment with pembrolizumab to confirmed PSA progression per PCWG3.

Time from first treatment with pembrolizumab to radiographic progression per PCWG3 and RECIST 1.1.

Time from first treatment with pembrolizumab to confirmed PSA progression per PCWG3 or death.

Time from first treatment with pembrolizumab to radiographic progression per PCWG3 and RECIST 1.1 or death.

Time from first treatment with pembrolizumab to death.

Time from first treatment with pembrolizumab to day 1 of the next systemic prostate cancer therapy.

All adverse events and their relationships to study drugs and procedures will be recorded.

Spots Global Cancer Trial Database for programmed cell death protein 1