Abiraterone Dosing for Prostate Cancer

Overseen By Cancer Clinical Trials Intak

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Chicago

Must be taking: Abiraterone, Prednisone

Must not be taking: Hormonal therapy, CYP3A4 drugs

Disqualifiers: Uncontrolled hypertension, Heart failure, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you must stop any other anticancer therapies and certain hormonal therapies at least 28 days before starting the study drug. However, medications like denosumab or zoledronic acid are allowed.

What data supports the effectiveness of the drug Abiraterone Oral Tablet for prostate cancer?

Research shows that Abiraterone, when combined with prednisone, significantly improves survival and delays disease progression in patients with metastatic castration-resistant prostate cancer, especially after chemotherapy. It works by blocking an enzyme needed for testosterone production, which helps slow the growth of prostate cancer. ^{1 2 3 4 5}

Is abiraterone safe for human use?

Abiraterone, used with prednisone, is generally safe for treating prostate cancer, but it can cause side effects like heart issues, liver problems, and changes in hormone levels, leading to fluid retention and high blood pressure. Regular monitoring and management of these side effects are important during treatment. ^{1 2 6 7 8}

What makes the drug Abiraterone with Prednisone unique for prostate cancer treatment?

Abiraterone with Prednisone is unique because it specifically blocks an enzyme needed for testosterone production, which helps slow the growth of prostate cancer. This combination is taken orally and is effective in both chemotherapy-naïve patients and those who have already received chemotherapy, offering a flexible treatment option for different stages of metastatic prostate cancer. ^{2 8 9 10 11}

What is the purpose of this trial?

Doctors leading this study plan to collect new information about the lowest effective dose of abiraterone acetate in study participants with prostate cancer who are taking abiraterone in combination with prednisone for the first time. The duration of this study will be about 3 months (12 weeks). How long you stay on abiraterone, and at what dose after completion of the 12 weeks of study drug administration, will be up to you and your treating physician.

Research Team

Russell Szmulewitz, MD

Principal Investigator

University of Chicago

Eligibility Criteria

Men with confirmed prostate cancer who are starting abiraterone and prednisone treatment for the first time can join. They must have not used similar drugs before, have a specific baseline hormone level, normal liver function, and be in good enough health to perform daily activities. Those with uncontrolled blood pressure, low potassium levels, serious heart conditions or infections, or taking certain other medications cannot participate.

Inclusion Criteria

I am taking Denosumab or Zoledronic acid.

I have never taken abiraterone or similar prostate cancer drugs.

I haven't had any radiotherapy or radionuclide treatments in the last 28 days.

Exclusion Criteria

I cannot swallow pills or have a condition that affects how my body absorbs food.

Serum K+ < 3.5 mmoL/L. Patients with a K+ < 3.5 mmoL/L are required to have a documented subsequent K+ >3.5 prior to enrollment to be eligible

Active psychiatric illness/social situations that would limit compliance with protocol requirements

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abiraterone 500 mg and prednisone 5 mg in various dosing regimens to determine the lowest effective dose

12 weeks

Weekly visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Abiraterone Oral Tablet
• Prednisone

Trial Overview The study is testing the lowest effective dose of abiraterone acetate (500 mg) taken orally by men with prostate cancer over a period of 12 weeks. Participants will also take prednisone and keep a drug diary while eating low-fat meals. The focus is on finding the minimum dose that still provides benefits.

Participant Groups

Group I: Group 4: Dose Regimen 4 Experimental Treatment 4 Interventions

You will be enrolled in the study based on the study group that is open at that particular time. If you are enrolled in this group, you will receive: - Abiraterone 500 mg and prednisone 5mg with a low-fat meal on day 1 of every week You will take 2 pills (500 mg total) of abiraterone acetate, first thing in the morning with breakfast. The tablets should be swallowed whole and not crushed, chewed, or dissolved in water. This breakfast should be a low-fat meal (avoid high calorie foods with a high percentage of fat, such as bacon or sausage). You will be asked to document the details of the meal/taking abiraterone in a daily log. You will also take prednisone 5 mg daily in the form of tablets taken by mouth with approximately 8 ounces of water with food. You do not have to take prednisone and abiraterone at the same time of day. If you inadvertently miss a dose of the study drug, you should take the dose the next day and record this on your Drug Diary.

Group II: Group 3: Dose Regimen 3 Experimental Treatment 4 Interventions

You will be enrolled in the study based on the study group that is open at that particular time. If you are enrolled in this group, you will receive: - Abiraterone 500 mg and prednisone 5mg with a low-fat meal on day 1 and day 4 of every week You will take 2 pills (500 mg total) of abiraterone acetate, first thing in the morning with breakfast. The tablets should be swallowed whole and not crushed, chewed, or dissolved in water. This breakfast should be a low-fat meal (avoid high calorie foods with a high percentage of fat, such as bacon or sausage). You will be asked to document the details of the meal/taking abiraterone in a daily log. You will also take prednisone 5 mg daily in the form of tablets taken by mouth with approximately 8 ounces of water with food. You do not have to take prednisone and abiraterone at the same time of day. If you inadvertently miss a dose of the study drug, you should take the dose the next day and record this on your Drug Diary.

Group III: Group 2: Dose Regimen 2 Experimental Treatment 4 Interventions

You will be enrolled in the study based on the study group that is open at that particular time. If you are enrolled in this group, you will receive: - Abiraterone 500 mg and prednisone 5mg with a low-fat meal on day 1, day 3, day 5 of every week You will take 2 pills (500 mg total) of abiraterone acetate, first thing in the morning with breakfast. The tablets should be swallowed whole and not crushed, chewed, or dissolved in water. This breakfast should be a low-fat meal (avoid high calorie foods with a high percentage of fat, such as bacon or sausage). You will be asked to document the details of the meal/taking abiraterone in a daily log. You will also take prednisone 5 mg daily in the form of tablets taken by mouth with approximately 8 ounces of water with food. You do not have to take prednisone and abiraterone at the same time of day. If you inadvertently miss a dose of the study drug, you should take the dose the next day and record this on your Drug Diary.

Group IV: Group 1: Dose Regimen 1 Experimental Treatment 4 Interventions

You will be enrolled in the study based on the study group that is open at that particular time. If you are enrolled in this group, you will receive: - Abiraterone 500 mg and prednisone 5mg with a low-fat meal every other day. You will take 2 pills (500 mg total) of abiraterone acetate, first thing in the morning with breakfast. The tablets should be swallowed whole and not crushed, chewed, or dissolved in water. This breakfast should be a low-fat meal (avoid high calorie foods with a high percentage of fat, such as bacon or sausage). You will be asked to document the details of the meal/taking abiraterone in a daily log. You will also take prednisone 5 mg daily in the form of tablets taken by mouth with approximately 8 ounces of water with food. You do not have to take prednisone and abiraterone at the same time of day. If you inadvertently miss a dose of the study drug, you should take the dose the next day and record this on your Drug Diary.

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Findings from Research

In a study of 131 patients with high-risk, nonmetastatic, castration-resistant prostate cancer, treatment with abiraterone acetate and prednisone resulted in an impressive 86.9% of patients achieving a 50% or greater reduction in prostate-specific antigen (PSA) levels, indicating strong efficacy.

The treatment also showed promising secondary outcomes, with a median time to PSA progression of 28.7 months, while safety was generally acceptable, although 96.2% of patients experienced adverse events, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The IMAAGEN Study: Effect of Abiraterone Acetate and Prednisone on Prostate Specific Antigen and Radiographic Disease Progression in Patients with Nonmetastatic Castration Resistant Prostate Cancer. Ryan, CJ., Crawford, ED., Shore, ND., et al.[2021]

In a pivotal phase III trial, oral abiraterone acetate combined with prednisone significantly improved overall survival and delayed disease progression in patients with metastatic castration-resistant prostate cancer (CRPC) who had previously undergone docetaxel chemotherapy.

While abiraterone acetate showed a generally acceptable safety profile, it was associated with higher rates of specific adverse events, such as cardiac disorders and fluid retention, compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: in metastatic castration-resistant prostate cancer. Yang, LP.[2021]

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]

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]

In a study of 95 metastatic castration-resistant prostate cancer (mCRPC) patients, 52% experienced potential drug-drug interactions (DDI) with abiraterone acetate, highlighting the prevalence of polypharmacy in this population.

Patients experiencing pain and those with poorer performance status were found to be at a higher risk for these interactions, suggesting that careful medication reviews by pharmacists are essential to minimize DDI risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential drug-drug interactions with abiraterone in metastatic castration-resistant prostate cancer patients: a prevalence study in France. Bonnet, C., Boudou-Rouquette, P., Azoulay-Rutman, E., et al.[2017]

In a phase III trial involving men with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate combined with prednisone significantly improved overall survival and radiographic progression-free survival compared to placebo.

The incidence of corticosteroid-related adverse events was similar between the treatment and placebo groups, indicating that while monitoring for side effects is necessary, the benefits of improved survival with abiraterone acetate plus prednisone outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate and prednisone in chemotherapy-naïve prostate cancer patients: rationale, evidence and clinical utility. Crawford, ED., Shore, ND., Petrylak, DP., et al.[2020]

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]

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]

References

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

The IMAAGEN Study: Effect of Abiraterone Acetate and Prednisone on Prostate Specific Antigen and Radiographic Disease Progression in Patients with Nonmetastatic Castration Resistant Prostate Cancer. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: in metastatic castration-resistant prostate cancer. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

The Phase 3 COU-AA-302 Study of Abiraterone Acetate Plus Prednisone in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Stratified Analysis Based on Pain, Prostate-specific Antigen, and Gleason Score. [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. Australia pubmed.ncbi.nlm.nih.gov

Abiraterone acetate for metastatic castration-resistant prostate cancer after docetaxel failure: A randomized, double-blind, placebo-controlled phase 3 bridging study. [2022]

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

Abiraterone-Induced Endocrinopathies. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Potential drug-drug interactions with abiraterone in metastatic castration-resistant prostate cancer patients: a prevalence study in France. [2017]

8. England pubmed.ncbi.nlm.nih.gov

Abiraterone acetate and prednisone in chemotherapy-naïve prostate cancer patients: rationale, evidence and clinical utility. [2020]

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

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. [2022]

10. United States 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. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Abiraterone in heavily pretreated patients with metastatic castrate-resistant prostate cancer. [2016]