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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the lowest effective dose of abiraterone acetate (an oral tablet) for people with prostate cancer. Participants will take abiraterone with prednisone and follow different dosing schedules to determine the most effective regimen. Those with prostate cancer who have not used abiraterone or similar medications may qualify. The goal is to gather information to help tailor treatments for future patients. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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.

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

Research shows that abiraterone, when combined with prednisone, is generally safe for prostate cancer patients. Most participants in past studies taking abiraterone experienced at least one side effect, but serious issues were less common compared to standard treatments. Specifically, 64.1% of patients had serious side effects with abiraterone, slightly lower than those on standard care.

Abiraterone has shown promising results in clinical trials, with many studies achieving their goals. Lower doses of abiraterone have even been linked to better survival rates in prostate cancer patients. Regarding prednisone, research suggests that low doses, such as 5 mg daily, are generally safe.

In summary, abiraterone with prednisone is well-tolerated by many patients, and safety data from previous studies support its use. However, like any treatment, there are risks of side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about abiraterone in this trial because it offers a unique dosing approach for prostate cancer treatment. Unlike the standard treatments that might require daily administration, abiraterone in this trial is being tested with less frequent dosing regimens, potentially improving patient convenience and adherence. The trial also explores the combination with prednisone, aiming to enhance efficacy while possibly reducing side effects. By adjusting the frequency and pairing with a low-fat meal, this approach might offer a more patient-friendly option without compromising effectiveness.

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

Research has shown that a lower dose of abiraterone can be as effective as a higher dose for treating prostate cancer. Specifically, a 500 mg dose of abiraterone acetate works similarly to the usual 1,000 mg dose. In this trial, participants will follow different dosing regimens to assess the effectiveness of these lower doses. Studies have found that over 60% of patients experienced a significant drop in prostate-specific antigen (PSA) levels, indicating positive cancer control. Another study discovered that a lower dose provided similar cancer control in men with advanced prostate cancer. These findings suggest that lower doses might effectively manage prostate cancer while potentially reducing side effects. ^{4 6 7 8 9}

Who Is on the Research Team?

Russell Szmulewitz, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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 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]

Citations

1. urologytimes.com urologytimes.com/view/lower-dose-of-abiraterone-shows-comparable-efficacy-to-standard-dose-for-prostate-cancer

Lower dose of abiraterone shows comparable efficacy to ... A 500 mg dose of abiraterone acetate showed comparable efficacy to the standard 1000 mg dose in prostate cancer treatment, with a favorable ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40902131/

Low-Dose Abiraterone in Metastatic Castration-Resistant ... Abiraterone acetate (AA) is approved for prostate cancer at a standard dose of 1,000 mg fasting. Because of a significant food effect, a lower dose (250 mg ...

3. ecancer.org ecancer.org/en/news/26791-lower-dose-of-abiraterone-acetate-as-effective-for-prostate-cancer-treatment

Lower dose of abiraterone acetate as effective for prostate ... In their study involving nine men with metastatic prostate cancer, they found that this lower dose resulted in comparable cancer suppression.

4. ascopubs.org ascopubs.org/doi/10.1200/GO-25-00132

Low-Dose Abiraterone in Metastatic Castration-Resistant ... AALD achieved a ≥50% prostate-specific antigen (PSA) response rate at 12 weeks in over 60% of patients and at PSA nadir in nearly 70%. Median ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1130634325001023

Low-dose abiraterone acetate for the treatment of prostate ... This study provides evidence supporting the use of low-dose abiraterone in patients with metastatic prostate cancer, showing survival and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40940844/

The Safety of Abiraterone Acetate in Patients with Metastatic ... Nearly all participants experienced at least one adverse event (98.4% abiraterone, 97.3% standard of care [SOC]).

7. mdpi.com mdpi.com/2072-6694/17/17/2747

The Safety of Abiraterone Acetate in Patients with ... More serious adverse events (grade 3 or 4) and deaths (grade 5) occurred in those receiving SOC (71.8%) compared to abiraterone (64.1%). The most frequent ...

8. e-juo.org e-juo.org/journal/view.php?number=594

Assessing Patient Risk, Benefit, and Outcomes in Drug ... Nearly all clinical trials testing abiraterone in prostate cancer showed promising outcomes with 89% of studies meeting their endpoint.

9. 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.