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

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

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

Study Overview

• Status: Recruiting
• Conditions: Metastatic Prostate Cancer; Prostate Cancer (Adenocarcinoma)
• Intervention / Treatment: Drug: Abiraterone acetate; Drug: Dexamethasone; Drug: Metronidazole

Detailed Description

To test whether giving dexamethasone with or without metronidazole in combination with abiraterone could help reverse resistance to abiraterone for patients with metastatic castration-resistant prostate cancer (mCRPC). Abiraterone and prednisone (AA/P) is a second-line therapy for mCRPC given when first-line androgen deprivation therapy fails. However, resistance to AA/P can develop. The investigators do not know exactly how cancer becomes resistant, but there is evidence that suggests it could be due to androgen production by the bacteria in your gut (gut microbiome). This study is focused on the gut microbiome as a source of androgen production that could cause AA/P resistance in mCRPC.

• Study Type: Interventional
• Enrollment (Estimated): 58
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Donna Bieg, RN; Phone Number: 410-502-7635; Email: dieg2@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Recruiting
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
      • Contact: Irina Rifkind, RN; Phone Number: 410-502-2043; Email: Irifkin1@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 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

Exclusion Criteria:

• 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.
• 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 the subject at risk, or interfere with the subject's participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Abiraterone + Dexamethasone; Abiraterone acetate plus dexamethasone	Drug: Abiraterone acetate; Abiraterone acetate 1000mg/ day; Drug: Dexamethasone; Dexamethasone 0.5mg/day
Experimental: Arm 2: Abiraterone + Dexamethasone + metronidazole; Abiraterone acetate plus dexamethasone plus metronidazole	Drug: Abiraterone acetate; Abiraterone acetate 1000mg/ day; Drug: Dexamethasone; Dexamethasone 0.5mg/day; Drug: Metronidazole; Metronidazole 1500mg/ per day; Other Names: Flagyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with PSA50 response	Number of participants with castration resistant prostate cancer who have a ≥ 50% decline in PSA from baseline until 12 weeks.	12 weeks
PSA Progression Free Survival	Number of participants with PSA progression according to PCWG3 (25% rise in PSA from nadir and increase of at least 2ng/mL)	12 weeks
Number of participants with progression	progression is defined as: Progression of soft tissue lesions according to RECIST 1.1 Criteria.; Progression of bone lesions detected with bone scan according to PCWG3 criteria.; Radiologically-confirmed spinal cord compression or pathological fracture due to malignant progression, or other clinical event deemed to be cancer-related, or death.	24 weeks
Number of grade 3-5 toxicities	Toxicity is evaluated based on current CTCAE standard grading scales.	24 weeks

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: United States Department of Defense; Prostate Cancer Foundation
• Investigators: Principal Investigator: Catherine Handy Marshall, M.D., Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2025
• Primary Completion (Estimated): March 30, 2031
• Study Completion (Estimated): March 30, 2032

Study Registration Dates

• First Submitted: September 23, 2024
• First Submitted That Met QC Criteria: September 26, 2024
• First Posted (Actual): September 27, 2024

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Dexamethasone; microbiome; Abiraterone
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Prostatic Neoplasms; Adenocarcinoma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Polycyclic Compounds; Imidazoles; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Androstenes; Androstanes; Nitroimidazoles; Nitro Compounds; Abiraterone Acetate; Dexamethasone; Metronidazole
• Other Study ID Numbers: J2485; IRB00453879 (Other Identifier: JHM IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No