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

Phase 2

Recruiting

• Conditions: Prostate Cancer (Adenocarcinoma); Metastatic Prostate Cancer
• Interventions: Drug: Abiraterone acetate; Drug: Dexamethasone; Drug: Metronidazole

• Registration Number: NCT06616597
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Study Timeline

• Study First Submitted: 2024-09-23
• Study First Submitted QC: 2024-09-26
• Study First Posted: 2024-09-27
• Status Verified: 2025-02
• Study Start: 2025-02-13
• Last Update Submitted: 2025-02-28
• Last Update Posted: 2025-03-05
• Primary Completion: 2031-03-30
• Study Completion: 2032-03-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 58

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 1: Abiraterone + Dexamethasone	Abiraterone acetate	Abiraterone acetate plus dexamethasone
Arm 1: Abiraterone + Dexamethasone	Dexamethasone	Abiraterone acetate plus dexamethasone
Arm 2: Abiraterone + Dexamethasone + metronidazole	Abiraterone acetate	Abiraterone acetate plus dexamethasone plus metronidazole
Arm 2: Abiraterone + Dexamethasone + metronidazole	Dexamethasone	Abiraterone acetate plus dexamethasone plus metronidazole
Arm 2: Abiraterone + Dexamethasone + metronidazole	Metronidazole	Abiraterone acetate plus dexamethasone plus metronidazole

Primary Outcome Measures

Name	Time	Method
Number of participants with PSA30 response	24 weeks	Number of participants with castration resistant prostate cancer who have a ≥ 30% decline in PSA from baseline until 24 weeks.

Secondary Outcome Measures

Name	Time	Method
Number of participants with PSA50 response	12 weeks	Number of participants with castration resistant prostate cancer who have a ≥ 50% decline in PSA from baseline until 12 weeks.
PSA Progression Free Survival	12 weeks	Number of participants with PSA progression according to PCWG3 (25% rise in PSA from nadir and increase of at least 2ng/mL)
Number of participants with progression	24 weeks	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.
Number of grade 3-5 toxicities	24 weeks	Toxicity is evaluated based on current CTCAE standard grading scales.

Trial Locations

Locations (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States