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.

Merck Sharp & Dohme LLC

Prostate Cancer Foundation

Johns Hopkins University

Oregon Health and Science University

Julie Graff, MD

Section Chief-Hematology and Oncology

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Mesothelioma

Mesothelioma, Malignant

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Malignant Mesothelioma

Immunomodulating Agents

The patient will undergo fecal microbiota transplant. The 600cc of donor stool will be transplanted by colonoscopy.

Fecal material from a healthy family donor will be transplanted into the patient via colonoscopy

Fecal Microbiota Transplant

The investigators propose to ensure a favorable gut microbiome by fecal microbiota transplant to enhance the efficacy Keytruda

Studies have shown that a favorable microbiome can be the difference between response and non-response of certain cancer treatments such as PD-1 blockade inhibitors. As such the investigators propose to ensure a favorable microbiome in this patient by fecal microbiota transplant to enhance the efficacy of such a drug, Keytruda.

A Single Dose FMT Infusion as an Adjunct to Keytruda for Metastatic Mesothelioma

A Single Dose FMT Infusion From a Healthy Family Donor Via Colonoscopy as an Adjunct to Keytruda for the Benefit of Improving Efficacy of Immunotherapy for Metastatic Mesothelioma

The time from transplant that the patient's tumors remain stable or shrink.

ProgenaBiome

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Bevacizumab

Atezolizumab

Angiogenesis Inhibitors

Growth Inhibitors

Single FMT from patients with HCC who responded to PD-(L)1-based immunotherapy to patients with HCC who failed to achieve complete or partial response (according to mRECIST) to atezolizumab/bevacizumab. After single FMT, patients will continue to receive atezolizumab/bevacizumab every 21-days according to protocol.

FMT combined with Atezolizumab plus Bevacizumab

Matthias Pinter, MD PhD

Katharina Pomej, MD

Bernhard Scheiner, MD PhD

Adrian Frick, MD

Lorenz Balcar, MD

This single-center, pilot study (phase IIa) will evaluate the safety, feasibility, and efficacy of FMT from patients with HCC who responded to PD-(L)1-based immunotherapy to patients with HCC who failed to respond to atezolizumab/bevacizumab.

The main purpose of this phase IIa pilot study is to test the safety and efficacy of fecal microbiota transplant (FMT) combined with atezolizumab plus bevacizumab in patients who failed to respond to prior immunotherapy for advanced hepatocellular carcinoma (aHCC).

The primary objective is to assess the safety of FMT combined with atezolizumab plus bevacizumab, as measured by incidence and severity of treatment-related adverse events.

The secondary objectives are to assess the efficacy of FMT in combination with atezolizumab plus bevacizumab as measured by best radiological response, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Furthermore, the objective is to evaluate the impact of FMT with atezolizumab plus bevacizumab on the quality of life, as assessed by EQ-5D-5L questionnaires.

Finally, this study also aims to assess the following exploratory endpoints:

* the effect of FMT on recipient gut microbiota composition, diversity, rate of change from baseline, and similarity to donor stool composition over time (compared between responders and non-responders)
* the effect of FMT on immune activity in the gut
* metagenome assemblies and functional profiling before and after FMT
* single cell analyses of circulating immune cells before and after FMT
* serum and stool metabolomic and lipidomic signatures before and after FMT

This is a phase IIa, single-center, open-label pilot study. Twelve patients suffering from advanced-stage hepatocellular carcinoma will be enrolled in this trial. The planned duration for this study are 48 months.

12 Patients with HCC who failed to achieve a complete or partial response (according to mRECIST) to atezolizumab plus bevacizumab

FMT in IT-refractory HCC - FAB-HCC Pilot Study

Fecal Microbiota Transplant (FMT) Combined With Atezolizumab Plus Bevacizumab in Patients With HepatoCellular Carcinoma Who Failed to Respond to Prior Immunotherapy - the FAB-HCC Pilot Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Fecal Microbiota Transplant and Pembrolizumab for Men With Metastatic Castration Resistant Prostate Cancer.	NCT04116775	Prostate Cancer Prostate Cancer...	Fecal microbiot... Pembrolizumab Enzalutamide	18 Years -	Portland VA Medical Center
A Single Dose FMT Infusion as an Adjunct to Keytruda for Metastatic Mesothelioma	NCT04056026	Mesothelioma	Fecal Microbiot...	-	ProgenaBiome
FMT in IT-refractory HCC - FAB-HCC Pilot Study	NCT05750030	Hepatocellular ...	FMT combined wi...	18 Years -	Medical University of Vienna

Spots Global Cancer Trial Database for fecal microbiota transplant