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

NCT ID: NCT06616597

Last Updated: 2025-03-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-13
• Study Completion Date: 2032-03-30

Brief Summary

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

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.

Conditions

Prostate Cancer (Adenocarcinoma); Metastatic Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1: Abiraterone + Dexamethasone

Abiraterone acetate plus dexamethasone

Group Type: EXPERIMENTAL

Abiraterone acetate

Intervention Type: DRUG

Abiraterone acetate 1000mg/ day

Dexamethasone

Intervention Type: DRUG

Dexamethasone 0.5mg/day

Arm 2: Abiraterone + Dexamethasone + metronidazole

Abiraterone acetate plus dexamethasone plus metronidazole

Group Type: EXPERIMENTAL

Abiraterone acetate

Intervention Type: DRUG

Abiraterone acetate 1000mg/ day

Dexamethasone

Intervention Type: DRUG

Dexamethasone 0.5mg/day

Metronidazole

Intervention Type: DRUG

Metronidazole 1500mg/ per day

Interventions

Abiraterone acetate

Abiraterone acetate 1000mg/ day

Intervention Type: DRUG

Dexamethasone

Dexamethasone 0.5mg/day

Intervention Type: DRUG

Metronidazole

Metronidazole 1500mg/ per day

Intervention Type: DRUG

Other Intervention Names

Flagyl

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

Prostate Cancer Foundation

OTHER

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Catherine Handy-Marshall, M.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Irina Rifkind, RN

Role: CONTACT

Irifkin1@jhmi.edu

410-502-2043

Yelena Milman

Role: CONTACT

ymilman1@jhmi.edu

410-955-1865

Facility Contacts

Irina Rifkind, RN

Role: primary

Irifkin1@jhmi.edu

410-502-2043

Other Identifiers

IRB00453879

Identifier Type: OTHER

Identifier Source: secondary_id

J2485

Identifier Type: -

Identifier Source: org_study_id