Trial Targeting Gut Bacterial Androgen Production to Reverse Therapeutic Resistance to Abiraterone in Patients With Metastatic Prostate Cancer

Inclusion Criteria:

• Males aged 18 years of age and above.

• Prostate adenocarcinoma

• Absolute PSA ≥ 2.0 ng/mL at screening.

• PSA (+/- radiographic) progression after having been on abiraterone and prednisonefor at least 12 weeks.

• Must be maintained on a GnRH analogue or have undergone orchiectomy.

• Participants must have a life expectancy ≥ 6 months

• Ability to swallow study medication tablets

• Willing to abstain from alcohol during and for 14 days after treatment withmetronidazole

• Willing and able to collect urine and stool samples per protocol

Exclusion Criteria:

• Active infection or other medical condition that would make dexamethasone usecontraindicated

• Any chronic medical condition requiring a higher systemic dose of corticosteroid

• Pathological finding consistent with small cell carcinoma of the prostate

• Has imminent or established spinal cord compression based on clinical findingsand/or MRI.

• Chronic liver disease with Child-Pugh class C cirrhosis (see calculator in protocol)

• Bilirubin >3x ULN or AST and ALT >5x ULN

• Congenital prolonged QTc syndrome or QTc > 500 msec (non-paced rhythm)

• History of pituitary or adrenal dysfunction

• Uncontrolled diabetes (Hemoglobin A1c > 10%) or increasing doses of insulinwithin the past 4 weeks due to poorly controlled glucoses.

• Administration of an investigational therapeutic or invasive surgical procedure (notincluding surgical castration) within 30 days of Cycle 1 Day 1 or currently enrolledin an investigational drug study

• Any other serious illness or medical condition that would, in the opinion of theinvestigator, make this protocol unreasonably hazardous, including, but not limitedto:

• Any uncontrolled major infection.

• Crohn's disease or ulcerative colitis.

• Known or suspected toxic megacolon and/or known small bowel ileus.

• Known allergy to any of the compounds under investigation.

• On antibacterial therapy within 30 days prior to administration of study treatment.

• Any condition or situation which, in the opinion of the investigator, would put thesubject at risk, or interfere with the subject's participation in this study.