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

NCT06616597 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: J2485IRB00453879
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

To determine if dexamethasone or dexamethasone plus metronidazole restore sensitivity to abiraterone for the treatment of metastatic prostate cancer.

Conditions

Prostate Cancer (Adenocarcinoma); Metastatic Prostate Cancer

Keywords

Abiraterone; microbiome; Dexamethasone

Outcome Measures

Primary Outcomes (1)

• Number of participants with PSA30 response

  Number of participants with castration resistant prostate cancer who have a ≥ 30% decline in PSA from baseline until 24 weeks.

  24 weeks

Secondary Outcomes (4)

• Number of participants with PSA50 response

  12 weeks

• PSA Progression Free Survival

  12 weeks

• Number of participants with progression

  24 weeks

• Number of grade 3-5 toxicities

  24 weeks

Study Arms (2)

Arm 1: Abiraterone + Dexamethasone

EXPERIMENTAL

Abiraterone acetate plus dexamethasone

Drug: Abiraterone acetate; Drug: Dexamethasone

Arm 2: Abiraterone + Dexamethasone + metronidazole

EXPERIMENTAL

Abiraterone acetate plus dexamethasone plus metronidazole

Drug: Abiraterone acetate; Drug: Dexamethasone; Drug: Metronidazole

Interventions

Metronidazole DRUG

Metronidazole 1500mg/ per day

Also known as: Flagyl

Arm 2: Abiraterone + Dexamethasone + metronidazole

Abiraterone acetate DRUG

Abiraterone acetate 1000mg/ day

Arm 1: Abiraterone + Dexamethasone; Arm 2: Abiraterone + Dexamethasone + metronidazole

Dexamethasone DRUG

Dexamethasone 0.5mg/day

Arm 1: Abiraterone + Dexamethasone; Arm 2: Abiraterone + Dexamethasone + metronidazole

Eligibility Criteria

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

You may qualify if:

• 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 prednisone for 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 with metronidazole
• Willing and able to collect urine and stool samples per protocol

You may not qualify if:

• Active infection or other medical condition that would make dexamethasone use contraindicated
• 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 findings and/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 insulin within the past 4 weeks due to poorly controlled glucoses.
• Administration of an investigational therapeutic or invasive surgical procedure (not including surgical castration) within 30 days of Cycle 1 Day 1 or currently enrolled in an investigational drug study
• Any other serious illness or medical condition that would, in the opinion of the investigator, make this protocol unreasonably hazardous, including, but not limited to:
• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• United States Department of Defense: collaborator
• Prostate Cancer Foundation: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms; Adenocarcinoma

Interventions

Abiraterone Acetate; Dexamethasone; Metronidazole

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids, Fluorinated; Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Catherine Handy Marshall, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Donna Bieg, RN

CONTACT

410-502-7635; dieg2@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2024
• First Posted: September 27, 2024
• Study Start: February 13, 2025
• Primary Completion (Estimated): March 30, 2031
• Study Completion (Estimated): March 30, 2032
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)