Metronidazole + Abiraterone + Dexamethasone for Prostate Cancer

Recruiting at1 trial location

Overseen by Catherine Handy-Marshall, M.D.

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must be taking: GnRH analogues

Must not be taking: Antibacterials

Disqualifiers: Infections, Liver disease, Diabetes, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not be on antibacterial therapy within 30 days before starting the study treatment. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Metronidazole + Abiraterone + Dexamethasone for prostate cancer?

Research shows that abiraterone acetate combined with prednisone improves survival in men with metastatic castration-resistant prostate cancer. Additionally, switching from prednisone to dexamethasone may benefit patients who no longer respond to abiraterone and prednisone. ^{1 2 3 4 5}

Is the combination of Metronidazole, Abiraterone, and Dexamethasone safe for humans?

The safety of Dexamethasone and Abiraterone has been studied in prostate cancer treatments, showing they can be used safely in combination with other drugs like docetaxel. However, specific safety data for the combination with Metronidazole is not available in the provided research. ^{1 5 6 7 8}

How is the drug combination of Metronidazole, Abiraterone, and Dexamethasone unique for prostate cancer?

This drug combination is unique because it includes Metronidazole, which is not typically used in prostate cancer treatments, alongside Abiraterone and Dexamethasone. The inclusion of Metronidazole, commonly used for infections, may offer a novel approach to enhance the effectiveness of the other drugs in treating prostate cancer. ^{1 2 4 5 9}

Research Team

Catherine Handy-Marshall, M.D.

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for men with metastatic prostate cancer who have become resistant to abiraterone treatment. Specific eligibility criteria are not provided, but typically participants would need to be in good health otherwise and meet certain medical standards set by the study.

Inclusion Criteria

I have been diagnosed with prostate cancer.

Willing and able to collect urine and stool samples per protocol

Absolute PSA ≥ 2.0 ng/mL at screening

Exclusion Criteria

I have not taken antibiotics in the last 30 days.

My prostate cancer is diagnosed as small cell carcinoma.

I have severe liver disease (Child-Pugh class C).

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abiraterone with dexamethasone, with or without metronidazole, to test the reversal of resistance in metastatic prostate cancer

24 weeks

Regular visits as per trial protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dexamethasone (Corticosteroid)
• Metronidazole (Antibiotic)

Trial Overview The study is testing if adding dexamethasone alone or in combination with metronidazole can make abiraterone effective again for treating metastatic prostate cancer. It's a Phase II trial, which means it's looking at effectiveness and side effects.

Participant Groups

Group I: Arm 2: Abiraterone + Dexamethasone + metronidazole Experimental Treatment 3 Interventions

Abiraterone acetate plus dexamethasone plus metronidazole

Group II: Arm 1: Abiraterone + Dexamethasone Experimental Treatment 2 Interventions

Abiraterone acetate plus dexamethasone

Dexamethasone is already approved in Canada, Japan for the following indications:

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Dr. William G. Nelson

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Director since 1992

MD, PhD

Dr. Elizabeth Jaffee

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Chief Medical Officer since 2023

MD

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Pete Hegseth

United States Department of Defense

Chief Executive Officer

Bachelor's degree in Political Science from Princeton University, JD from Harvard Law School

Lisa Hershman

United States Department of Defense

Chief Medical Officer since 2021

MD from Uniformed Services University of the Health Sciences

Prostate Cancer Foundation

Collaborator

Trials

52

Recruited

3,000+

Findings from Research

Switching from prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer who have progressed on abiraterone acetate plus prednisone may be beneficial, as suggested by the review of four clinical studies.

Potential candidates for this steroid switch include patients with PSA progression but no clinical or radiological progression, those without severe side effects from CYP-17 inhibition, and individuals unfit for chemotherapy or radium-223.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticosteroid switch after progression on abiraterone acetate plus prednisone. Roviello, G., Sobhani, N., Corona, SP., et al.[2020]

In a phase 3 trial with 1088 patients, abiraterone acetate plus prednisone significantly improved overall survival compared to placebo plus prednisone, with a median survival of 34.7 months versus 30.3 months, indicating its efficacy in treating chemotherapy-naive castration-resistant prostate cancer.

The treatment was associated with a manageable safety profile, although there were some increased risks of grade 3-4 adverse events, such as cardiac disorders and elevated liver enzymes, suggesting that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Ryan, CJ., Smith, MR., Fizazi, K., et al.[2022]

Switching from prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer who have progressed on abiraterone acetate plus prednisone shows promising efficacy, with pooled rates of PSA50 and PSA30 at 24% and 42%, respectively.

The treatment is well-tolerated with no severe adverse events reported, suggesting that this steroid switch could be a safe and effective strategy for managing disease progression in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Steroid switch after progression on abiraterone plus prednisone in patients with metastatic castration-resistant prostate cancer: A systematic review. Xiong, X., Qiu, S., Yi, X., et al.[2022]

In the phase III COU-AA-301 study involving 1,195 patients with metastatic castration-resistant prostate cancer, higher baseline serum androgen levels, particularly testosterone, were strongly associated with improved overall survival, indicating that these levels can serve as a prognostic marker.

Abiraterone acetate combined with prednisone significantly prolonged overall survival compared to prednisone alone, regardless of baseline serum androgen levels, highlighting its efficacy as a treatment option for patients after docetaxel chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum androgens as prognostic biomarkers in castration-resistant prostate cancer: results from an analysis of a randomized phase III trial. Ryan, CJ., Molina, A., Li, J., et al.[2022]

Both docetaxel combined with androgen deprivation therapy (ADT) and abiraterone acetate with prednisone/prednisolone plus ADT have been shown to improve survival rates in patients with metastatic castration-naive prostate cancer.

The choice between these treatments should be personalized based on the individual characteristics of the patient, ensuring the best possible outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Castration-naive Metastatic Prostate Cancer. Hamilou, Z., Baciarello, G., Fizazi, K.[2019]

In a study of 40 patients with hormone-refractory prostate cancer, a sequential chemotherapy regimen using docetaxel and estramustine resulted in a significant PSA response, with 72.5% of patients achieving a decline of 50% or more in PSA levels.

Despite a favorable toxicity profile, the addition of mitoxantrone after docetaxel did not enhance treatment efficacy, indicating that while the sequential approach is safe, it may not improve outcomes compared to docetaxel alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of sequential chemotherapy with docetaxel-estramustine followed by mitoxantrone-prednisone in patients with advanced hormone-refractory prostate cancer. Galli, L., Fontana, A., Galli, C., et al.[2022]

In a phase II trial involving 76 chemotherapy-naïve patients with castration-resistant prostate cancer (CRPC), the combination of docetaxel and dexamethasone resulted in a high PSA response rate of 76.8%, indicating effective treatment.

While most patients tolerated the treatment well, hematotoxicity, particularly neutropenia, was a common adverse effect, highlighting the need for monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of docetaxel-based chemotherapy combined with dexamethasone 1 mg daily oral administration: JMTO Pca 10-01 phase II trial. Tanaka, N., Nishimura, K., Okajima, E., et al.[2022]

Adding docetaxel or abiraterone to androgen-deprivation therapy (ADT) significantly improves overall survival in men with newly diagnosed metastatic prostate cancer, based on evidence from multiple studies involving thousands of participants.

The strongest survival benefits from docetaxel are observed in patients with high-volume metastatic disease, while abiraterone also shows similar benefits in high-risk patients, indicating both treatments are effective options alongside ADT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing Anticancer Therapy in Metastatic Non-Castrate Prostate Cancer: American Society of Clinical Oncology Clinical Practice Guideline. Morris, MJ., Rumble, RB., Basch, E., et al.[2019]

In a study involving 1917 men with locally advanced or metastatic prostate cancer, the combination of abiraterone acetate and prednisolone with androgen-deprivation therapy (ADT) significantly improved overall survival compared to ADT alone, with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death.

The combination therapy also resulted in a much lower rate of treatment failure, with a hazard ratio of 0.29, meaning patients were less likely to experience disease progression compared to those receiving only ADT, although it was associated with a higher incidence of grade 3 to 5 adverse events (47% vs. 33%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. James, ND., de Bono, JS., Spears, MR., et al.[2023]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Corticosteroid switch after progression on abiraterone acetate plus prednisone. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Steroid switch after progression on abiraterone plus prednisone in patients with metastatic castration-resistant prostate cancer: A systematic review. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Serum androgens as prognostic biomarkers in castration-resistant prostate cancer: results from an analysis of a randomized phase III trial. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of Castration-naive Metastatic Prostate Cancer. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Phase II study of sequential chemotherapy with docetaxel-estramustine followed by mitoxantrone-prednisone in patients with advanced hormone-refractory prostate cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

The efficacy and safety of docetaxel-based chemotherapy combined with dexamethasone 1 mg daily oral administration: JMTO Pca 10-01 phase II trial. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Optimizing Anticancer Therapy in Metastatic Non-Castrate Prostate Cancer: American Society of Clinical Oncology Clinical Practice Guideline. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. [2023]