Abiraterone Therapy for Metastatic Castration Resistant Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase < 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must be taking: GnRH analogue

Must not be taking: Cyp 17 inhibitors

Disqualifiers: CNS metastases, Liver metastasis, Uncontrolled hypertension, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method of using abiraterone, a drug approved for treating metastatic prostate cancer. Researchers aim to determine if an on-and-off dosing pattern can extend the drug's effectiveness and help participants maintain their ability to perform daily tasks. The study seeks men with metastatic prostate cancer who are currently taking abiraterone, have experienced at least a 50% reduction in PSA levels (a marker used to monitor prostate cancer), and do not have significant cancer-related pain. As an Early Phase 1 trial, this research focuses on understanding how this treatment approach works in people, offering participants a chance to contribute to pioneering cancer care strategies.

Will I have to stop taking my current medications?

You may need to stop certain medications. The trial requires stopping any prostate cancer therapies, except for GnRH analogue therapy, at least 3 weeks before starting the study drugs. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that abiraterone, a drug for treating advanced prostate cancer, is generally safe for patients. Studies have found that long-term use of abiraterone is usually well-tolerated, particularly for patients who maintain heart health. Most patients do not experience serious side effects that worsen over time.

In one study, the group taking abiraterone reported fewer serious side effects compared to those receiving standard treatment. Serious side effects occurred in 64.1% of patients on abiraterone, compared to 71.8% in the standard treatment group, suggesting that abiraterone is relatively safe.

The FDA has already approved abiraterone for treating advanced prostate cancer at a specific dose, indicating it has passed safety tests for that use. However, this trial is testing a different administration method, which might have different effects. Overall, abiraterone has a good safety record for treating prostate cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Abiraterone Acetate is unique because it explores a strategic on-and-off approach to treatment for metastatic castration-resistant prostate cancer (mCRPC). Unlike the continuous administration of standard treatments like chemotherapy or traditional hormone therapies, this method involves pausing Abiraterone once a significant PSA reduction is achieved and restarting it when PSA levels rise again. Researchers are excited because this approach may help manage the disease effectively while potentially reducing side effects and improving patients' quality of life by minimizing drug exposure.

What is the effectiveness track record for Abiraterone Acetate in treating metastatic castration resistant prostate cancer?

Research has shown that abiraterone acetate effectively treats a type of prostate cancer that continues to grow even when testosterone levels are low. In one study, patients who took abiraterone lived longer, with half living more than 42 months. Abiraterone blocks the production of certain hormones that can promote prostate cancer growth. This treatment has also led to a significant drop in PSA levels, indicating its effectiveness. Participants in this trial will receive abiraterone acetate therapy. The study schedule involves stopping the FDA-approved abiraterone after achieving a favorable PSA response and restarting it when PSA levels return to pre-abiraterone levels. ^{4 6 7 8 9}

Who Is on the Research Team?

Jingsong Zhang, MD

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Are You a Good Fit for This Trial?

This trial is for men with metastatic castration-resistant prostate cancer who are minimally symptomatic and have seen a significant drop in PSA levels after standard abiraterone treatment. They should be able to perform daily activities, not require opioids for pain, and have no major health issues or recent surgeries.

Inclusion Criteria

Ability to give written informed consent

My prostate cancer is advanced but not causing major symptoms, and my PSA levels have dropped by at least 50% since starting abiraterone.

My prostate cancer diagnosis was confirmed through a tissue sample.

Exclusion Criteria

Inability to comply with protocol requirements

Treatment with any investigational compound within 30 days prior to the first dose of study drugs

My cancer has spread to my brain or liver.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adaptive abiraterone therapy, with cycles defined by PSA response

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone Acetate

Trial Overview The study tests if taking abiraterone on an intermittent schedule can extend the drug's effectiveness in controlling prostate cancer while maintaining patients' ability to carry out everyday tasks.

How Is the Trial Designed?

Group I: Abiraterone Acetate Therapy Experimental Treatment 1 Intervention

Study schedule involves stopping FDA Approved abiraterone after participants achieve a good PSA response (50% or more decline of pre-abiraterone PSA) and then restarting abiraterone after their PSA reaches the level of pre-abiraterone PSA.

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?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

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]

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]

A study involving 32 healthy male subjects demonstrated that the test product (abiraterone acetate tablet) is bioequivalent to the reference product ZYTIGA® in terms of pharmacokinetics, with both products showing similar maximum concentration (Cmax) and area under the curve (AUC) values within the acceptable range.

The research confirmed significant intra-subject variability in the pharmacokinetics of abiraterone, indicating that individual responses to the drug can vary widely, which is important for clinicians to consider when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. Wang, C., Hu, C., Gao, D., et al.[2022]

Abiraterone acetate, in combination with prednisone, received full FDA approval for treating metastatic castration-resistant prostate cancer (mCRPC) based on the COU-AA-302 trial, which involved 1,088 patients and showed a significant improvement in radiographic progression-free survival (rPFS) compared to placebo (8.3 months vs. not reached).

The trial also indicated a favorable trend in overall survival (OS) for patients receiving abiraterone acetate, although it did not reach statistical significance, confirming the drug's efficacy and safety profile consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary. Kluetz, PG., Ning, YM., Maher, VE., et al.[2018]

Abiraterone acetate (Zytiga®) is an effective antiandrogen for prostate cancer but has poor oral bioavailability (<10%) and requires patients to fast around its administration due to a significant food effect (5-10-fold increase in absorption).

The review highlights the need for improved oral formulation strategies to enhance solubility and bioavailability of abiraterone acetate, aiming to reduce the required dose and eliminate the food effect, which could lead to better patient compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate. Schultz, HB., Meola, TR., Thomas, N., et al.[2020]

In a Swedish observational study of 119 patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate treatment resulted in similar overall survival rates compared to those seen in the pivotal clinical trial, despite a shorter median treatment duration of 5.6 months versus 7.3 months in the trial.

The findings suggest that while Swedish patients may have characteristics that could limit their treatment benefits, they still achieve comparable survival outcomes, indicating a potentially more cost-effective use of abiraterone in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value of treatment in clinical trials versus the real world: the case of abiraterone acetate (Zytiga) for postchemotherapy metastatic castration-resistant prostate cancer patients in Sweden. Svensson, J., Andersson, E., Persson, U., et al.[2017]

Oral abiraterone acetate (Zytiga®) effectively inhibits androgen biosynthesis, which is crucial for the progression of metastatic castration-resistant prostate cancer (mCRPC), and has been shown to prolong overall survival and radiographic progression-free survival in large phase 3 trials.

In combination with prednisone, abiraterone acetate has a manageable safety profile and is a convenient once-daily treatment option, making it a significant first-line therapy for men with mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone Acetate: A Review in Metastatic Castration-Resistant Prostrate Cancer. Scott, LJ.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10283214/

Survival outcomes and prognostic factors for first-line ... In this present study, the median OS for patients who received first-line abiraterone was 42.1 months (IQR 20.6–63.7), which was longer than the ...

2. waocp.com waocp.com/journal/index.php/apjcb/article/view/1482

Real-World Clinical Outcomes of Low Dose versus ... Low-dose abiraterone seems to be comparable to standard-dose abiraterone in mCRPC with 75% lower financial cost.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24508071/

Outcomes with abiraterone acetate in metastatic castration- ... Conclusions: ECOG PS ≥2 mCRPC patients treated with abiraterone have inferior outcomes compared with ECOG 0-1 patients, especially in regard to OS. These data ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1209096

Abiraterone in Metastatic Prostate Cancer without Previous ... Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)36668-2/fulltext

Clinical activity of abiraterone acetate in patients with ... Median overall survival was 50.1 weeks (95% CI 28.3–72.0). Three patients had a ≥30% PSA decline with abiraterone. Two of these patients had PSA progression as ...

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

The Safety of Abiraterone Acetate in Patients with Metastatic ... A real-world prospective study is warranted to examine the overall risks and benefits associated with treatment. Keywords: fracture; metastatic ...

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

The Safety of Abiraterone Acetate in Patients with ... The current study found that more serious adverse events occurred more frequently in the SOC group (71.8%) than in the abiraterone acetate group (64.1%). Odds ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4981293/

Safety of long-term exposure to abiraterone acetate in patients ... Long-term abiraterone treatment was well tolerated in mCRPC patients with controlled cardiovascular comorbidities/risk factors, with no apparent worsening of ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2468294218300583

Abiraterone in metastatic castration-resistant prostate cancer AA combined with low doses of prednisone improves overall survival of patients treated for metastatic CRPC (mCRPC) before and after docetaxel [10], [11].