Metronidazole + Abiraterone + Dexamethasone for Prostate Cancer

Recruiting at 1 trial location

Overseen By Yelena Milman

Age: 18+

Sex: Male

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

58 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding dexamethasone (a corticosteroid) or dexamethasone with metronidazole (an antibiotic) can help treat metastatic prostate cancer in men who no longer respond to abiraterone. It tests two treatment groups: one with abiraterone and dexamethasone, and the other with abiraterone, dexamethasone, and metronidazole. Men with prostate cancer that has spread and stopped responding to previous treatments might be suitable candidates, especially if their PSA levels (a prostate health marker) have risen. Participants should be able to swallow tablets, avoid alcohol during the study, and be willing to provide urine and stool samples. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining dexamethasone and abiraterone has been studied for treating prostate cancer. These studies indicate that the combination is generally safe when used with other drugs. Reports on abiraterone highlight its safety in many prostate cancer trials, with most showing positive results.

The addition of metronidazole to dexamethasone and abiraterone remains under investigation. Both dexamethasone and metronidazole are well-known medications. Dexamethasone often reduces swelling, while metronidazole serves as an antibiotic. These drugs are usually well-tolerated in other treatments.

The current trial is in an early stage, so information on the safety of this specific combination is limited. However, the individual drugs have a known safety record. This is encouraging, but it is important to remember that every treatment can have side effects. Participants should discuss any concerns with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they combine abiraterone with dexamethasone, and introduce metronidazole, which isn't typically used in standard prostate cancer therapies. Most treatments target hormone pathways, but this combination may enhance treatment effectiveness by potentially addressing additional biological pathways. The addition of metronidazole could offer a novel mechanism that makes cancer cells more susceptible to the existing drugs, possibly leading to improved outcomes. This innovative approach aims to provide a more comprehensive attack on the cancer, which could translate into better patient responses compared to the current standard of care.

What evidence suggests that this trial's treatments could be effective for metastatic prostate cancer?

Research has shown that combining abiraterone with dexamethasone effectively treats advanced prostate cancer. Studies have found that this combination significantly lowers prostate-specific antigen (PSA) levels in many patients, indicating treatment effectiveness. In this trial, one group of participants will receive abiraterone and dexamethasone, while another group will receive abiraterone, dexamethasone, and metronidazole. Adding metronidazole might enhance the treatment's effectiveness by overcoming resistance to abiraterone. This combination has been linked to a reduced risk of cancer progression. Overall, these treatments offer promising options for patients with advanced prostate cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Catherine Handy-Marshall, M.D.

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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).

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• Metronidazole

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.

How Is the Trial Designed?

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 European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

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+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Prostate Cancer Foundation

Collaborator

Trials

52

Recruited

3,000+

Published Research Related to This Trial

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]

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]

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]

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 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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6604092/

Assessment of the Safety of Glucocorticoid Regimens in ... This open-label, phase 2 randomized clinical trial assesses the safety of abiraterone acetate combined with 4 glucocorticoid regimens for treatment of ...

2. cda-amc.ca cda-amc.ca/sites/default/files/DRR/2023/PX0298/Clinical%20and%20Pharmacoeconomic%20Combined%20Report.pdf

Abiraterone Acetate and Prednisone or Dexamethasone ... CRPC-free survival and prostate cancer–specific survival were secondary outcomes in the PEACE-1 trial ... [Search terms -- abiraterone AND castration-sensitive ...

3. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-021-08670-2

Corticosteroid switch from prednisone to dexamethasone in ... Their study showed a prostate-specific antigen (PSA) decline of ≥50% (PSA50) in 51% of patients, whereas a PSA50 rate of 43% was observed in ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01867710

Study Details | NCT01867710 | Abiraterone With Different ... The purpose of the study is to determine the safety and clinical benefit of the combinations of abiraterone acetate and prednisone or abiraterone and ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2059702922000527

Real-world experience of abiraterone acetate plus ... In 481 chemotherapy-naive mCRPC patients (median follow-up: 25 months), abiraterone plus prednisone was effective and safe.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31246234/

A Randomized, Open-label Phase 2 Study Abiraterone acetate in combination with dexamethasone appeared to be particularly active but may be associated with adverse metabolic ...