Abiraterone + Niclosamide + Prednisone for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Mamta Parikh

Must be taking: LHRH agonists, LHRH antagonists

Must not be taking: Herbs, Alternative medicines

Disqualifiers: Chemotherapy, Radiotherapy, Brain metastases, 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: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a drug combination—abiraterone acetate, niclosamide, and prednisone—for treating prostate cancer unresponsive to hormone therapy. Abiraterone acetate reduces androgen, a hormone that can promote prostate cancer growth, while niclosamide, an antiparasitic drug, may block another growth signal. Prednisone reduces inflammation. This trial may suit men with prostate cancer that has progressed despite previous hormone treatments, particularly if they have rising PSA levels, a marker for prostate cancer activity. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 cannot participate if you have had chemotherapy or radiotherapy within 4 weeks before the study or are taking certain herbs or alternative medicines for prostate cancer. It's best to discuss your current medications with the trial team.

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

Research shows that the combination of abiraterone acetate, niclosamide, and prednisone is generally well-tolerated by people with prostate cancer. In earlier studies, patients taking abiraterone acetate and prednisone lived longer. Some side effects occurred, but they were usually manageable.

Studies found that when niclosamide was combined with abiraterone and prednisone, it reached the right levels in the blood and was well-tolerated. Patients taking these medications together did not experience severe side effects.

Overall, this combination of treatments has been studied and shown to be safe for many patients. Since this trial is in a later phase, the treatment has already been found safe in earlier tests. However, as with all medications, people may react differently, so discussing potential risks with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for prostate cancer because it brings together abiraterone acetate, niclosamide, and prednisone in a novel way. While abiraterone is already used to decrease testosterone levels, niclosamide stands out by targeting cancer cell growth through a completely different mechanism, potentially enhancing the effect of abiraterone. This combination could offer a more comprehensive approach to managing prostate cancer, as it simultaneously attacks the cancer through multiple pathways. By integrating these treatments, there's hope for improved outcomes and reduced disease progression compared to standard therapies like androgen deprivation therapy alone.

What evidence suggests that this treatment might be an effective treatment for hormone-resistant prostate cancer?

Studies have shown that taking abiraterone acetate with prednisone can extend the lives of patients with certain types of prostate cancer. Abiraterone reduces levels of androgens, hormones that can promote prostate cancer growth. Research suggests that niclosamide might block signals that enable cancer cells to grow, particularly in cases unresponsive to hormone therapy. In this trial, participants will receive a combination of abiraterone, niclosamide, and prednisone. Early findings indicate that this combination can be effective for patients with hormone-resistant prostate cancer. By attacking cancer growth in different ways, this approach may lead to better outcomes for patients. ^{1 3 5 6 7}

Who Is on the Research Team?

Mamta Parikh

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

Men with hormone-resistant prostate cancer, who have not had chemotherapy or radiotherapy in the last 4 weeks and have recovered from previous treatments. They must have a life expectancy over 6 months, be medically castrated with low testosterone levels, and agree to use contraception. Excluded are those with other recent cancers, brain metastases, severe illnesses that could affect study compliance or drug absorption issues.

Inclusion Criteria

Patients must have CaP deemed to be castration-resistant by one or more of the following criteria (despite androgen deprivation when applicable): - Progression of unidimensionally measurable disease assessed within 42 days prior to initial administration of drug - Progression of evaluable but not measurable disease assessed within 42 days prior to initial administration of drug for PSA evaluation and for imaging studies (e.g, bone scans) - Rising PSA, defined as at least two consecutive rises in PSA to be documented over a reference value (measure 1); the first rising PSA (measure 2) should be taken at least 7 days after the reference value; a third confirmatory PSA measure (second [2nd] beyond the reference level) should be greater than the second measure, and it must be obtained at least 7 days after the 2nd measure; if this is not the case, a fourth PSA measurement is required to be taken and be greater than the second measure - Measurable disease is not required - Patients who have measurable disease must have had X-rays, scans or physical examinations used for tumor measurement completed within 28 days prior to initial administration of drug - Patients must have non-measurable disease (such as nuclear medicine bone scans) and non-target lesions (such as PSA level) assessed within 28 days prior to initial administration of drug - Soft tissue disease that has been radiated within two months prior to registration is not assessable as measurable disease; soft tissue disease that has been radiated two or more months prior to registration is assessable as measurable disease provided that the lesion has progressed following radiation; as the biology of previously irradiated tumors may be different from non-irradiated tumors, patients must have at least one measurable lesion outside the previously irradiated region in order to be considered to have measurable disease - If PSA is the only indicator of disease and patients do not have any metastatic disease, PSA value must be 5.0 or higher - Patients must have been surgically or medically castrated; if the method of castration was luteinizing hormone-releasing hormone (LHRH) agonists (leuprolide or goserelin) or antagonists (degarelix), then the patient must be willing to continue the use of LHRH agonists or antagonists; serum testosterone must be at castration levels (< 50 ng/dL) within 3 months prior to registration - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) - Life expectancy of greater than 6 months - Leukocytes >= 3,000/mcL - Absolute neutrophil count >= 1,500/mcL - Platelets >= 100,000/mcL - Total bilirubin within normal institutional limits - Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 × institutional upper limit of normal - Creatinine =< 1.5 x institutional upper limit of normal - Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of abiraterone and PDMX1001/niclosamide administration - Ability to understand and the willingness to sign a written informed consent document

My prostate cancer is confirmed by tests and may be recurrent or has spread.

Exclusion Criteria

Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier - Patients who are receiving any other investigational agents within the preceding 4 weeks - Patients on herbs or other alternative medicines for the treatment of prostate cancer, including but not limited to saw palmetto, PC-SPES - Patient has received abiraterone or ketoconazole for the treatment of prostate cancer; however, previous treatment with other hormonal therapy (bicalutamide, enzalutamide, flutamide and nilutamide) or chemotherapy (docetaxel, cabazitaxel or mitoxantrone) is allowed - Other malignancies within the past 3 years except for adequately treated basal or squamous cell carcinomas of the skin or other stage 0 or I cancers - Patients with known brain metastases should be excluded - History of allergic reactions attributed to compounds of similar chemical or biologic composition to abiraterone or PDMX1001/niclosamide - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible - Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) - Patients with an active bleeding diathesis - History of noncompliance to medical regimens - Patients unwilling to or unable to comply with the protocol - Patients with symptomatic metastatic prostate cancer such as moderate to severe pain, impaired organ function or spinal cord compression will be excluded from this study unless these issues have been taken care of

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abiraterone acetate, niclosamide, and prednisone. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone Acetate
• Niclosamide
• Prednisone

Trial Overview The trial is testing the effectiveness of combining abiraterone acetate (lowers androgen production), niclosamide (blocks cancer cell growth signals), and prednisone (reduces inflammation) for treating hormone-resistant prostate cancer. It's a phase II trial to see how well these drugs work together.

How Is the Trial Designed?

Group I: Treatment (abiraterone acetate, niclosamide, prednisone) Experimental Treatment 3 Interventions

Patients receive abiraterone acetate PO QD, niclosamide PO BID and prednisone PO BID. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Abiraterone Acetate is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Metastatic high-risk castration-sensitive prostate cancer

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Newly diagnosed high-risk metastatic hormone-sensitive prostate cancer

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Metastatic castration-sensitive prostate cancer

Approved in Japan as Zytiga for:

• Prostate cancer

Who Is Running the Clinical Trial?

Mamta Parikh

Lead Sponsor

Trials

7

Recruited

210+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Oral abiraterone acetate (Zytiga®) significantly improves overall survival and progression-free survival in patients with metastatic castration-resistant prostate cancer (CRPC) when used with prednisone, compared to a placebo.

The treatment is specifically effective for patients who have already undergone docetaxel-containing chemotherapy, highlighting its role as a subsequent therapy in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. Scott, LJ., Yang, LPH., Lyseng-Williamson, KA.[2021]

In a phase 3 trial involving 1199 patients, the addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly improved overall survival, with a median survival not reached in the abiraterone group compared to 34.7 months in the placebo group.

The study also showed that patients receiving abiraterone had a median radiographic progression-free survival of 33.0 months, compared to 14.8 months in the placebo group, indicating a strong benefit in delaying disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. Fizazi, K., Tran, N., Fein, L., et al.[2022]

Abiraterone, when used with prednisone, improves overall and disease-free survival in patients with both castration-resistant and castration-sensitive prostate cancer.

In a case series of 3 patients, it was found that abiraterone can lead to mineralocorticoid excess and secondary adrenal insufficiency, highlighting the need for awareness and management of these endocrine side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone-Induced Endocrinopathies. Decamps, S., Lis, R., Ekanayake, P.[2023]

Abiraterone acetate (AA) combined with prednisone shows favorable safety and efficacy outcomes in treating metastatic prostate cancer, particularly in patients who are asymptomatic or have mild symptoms.

The treatment is generally well tolerated, but it is important to be aware of its known toxicity profile, including mineralocorticoid and corticosteroid-related adverse events, as well as hepatotoxicity, which can inform clinical decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A drug safety evaluation of abiraterone acetate in the treatment of prostate cancer. Castellan, P., Castellucci, R., Marchioni, M., et al.[2019]

In a clinical trial involving 164 men with metastatic castration-resistant prostate cancer, abiraterone acetate combined with prednisone (5 mg twice daily) or dexamethasone (0.5 mg once daily) effectively minimized mineralocorticoid excess, which is important for patient safety.

While abiraterone with dexamethasone showed promising efficacy, it was also linked to adverse metabolic effects, such as increased insulin resistance and decreased bone mineral density, highlighting the need for careful monitoring of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the Safety of Glucocorticoid Regimens in Combination With Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer: A Randomized, Open-label Phase 2 Study. Attard, G., Merseburger, AS., Arlt, W., et al.[2022]

In a study involving 1919 patients with metastatic prostate cancer, the addition of abiraterone acetate to standard androgen deprivation therapy significantly improved overall survival, with a median survival of 76.6 months compared to 45.7 months for standard care alone.

Combining both abiraterone and enzalutamide did not provide additional survival benefits over abiraterone alone, and it was associated with higher rates of severe side effects, suggesting that this combination should be avoided in long-term treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. Attard, G., Murphy, L., Clarke, NW., et al.[2023]

Abiraterone acetate significantly improves overall survival and radiographic progression-free survival in men with metastatic castration-resistant prostate cancer (CRPC) when combined with prednisone, based on results from a multinational phase III study involving men who had previously received docetaxel.

The treatment is generally well-tolerated, although it can cause side effects like hypokalaemia and hypertension; however, serious adverse events were relatively low in the phase III studies, indicating it is a viable option for managing metastatic CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a review of its use in patients with metastatic castration-resistant prostate cancer. Hoy, SM.[2021]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02807805

NCT02807805 | Abiraterone Acetate, Niclosamide, and ... Hormone therapy using abiraterone acetate may fight prostate cancer by lowering the amount of androgen the body makes. Niclosamide is a drug that may block ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10587977/

Real‑world survival outcome comparing abiraterone acetate ... Real‐world survival outcome comparing abiraterone acetate plus prednisone and enzalutamide for nonmetastatic castration‐resistant prostate cancer

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8105236/

Real-World Safety and Efficacy Outcomes with Abiraterone ... Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2468294223000060

Niclosamide in prostate cancer: An inhibitor of AR-V7, a ... A recent phase Ib study of reformulated niclosamide with abiraterone and prednisone in patients with advanced prostate cancer showed a promising preliminary ...

5. nature.com nature.com/articles/s41598-021-85969-x

Phase Ib trial of reformulated niclosamide with abiraterone ... A novel niclosamide/PDMX1001 reformulation achieved targeted plasma levels when combined with abiraterone and prednisone, and was well tolerated.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33826036/

Real-World Safety and Efficacy Outcomes with Abiraterone ... Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients.

7. europeanurology.com europeanurology.com/article/S0302-2838(25)00357-4/fulltext

Novel Therapeutic Strategies for Metastatic Prostate ... Phase Ib trial of reformulated niclosamide with abiraterone/prednisone in men with castration-resistant prostate cancer. Sci Rep. 2021; 11 ...