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

19 Participants Needed

Trial Summary

What is the purpose of this trial?

Abiraterone is approved in the United States by the U.S. Food and Drug Administration (FDA) to treat metastatic prostate cancer at 1000 mg daily. The purpose of this study is to find out if an on and off schedule of taking abiraterone would prolong the participant's cancer's response to this drug and maintain their functionality to perform their daily activities.

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.

What data supports the effectiveness of the drug Abiraterone Acetate (Zytiga) for metastatic castration-resistant prostate cancer?

In clinical trials, Abiraterone Acetate (Zytiga) combined with prednisone significantly improved overall survival and delayed disease progression in patients with metastatic castration-resistant prostate cancer compared to a placebo with prednisone. This drug is considered an important first-line option for this condition due to its effectiveness and manageable safety profile. ^{1 2 3 4 5}

Is abiraterone acetate safe for humans?

Abiraterone acetate, used with prednisone for prostate cancer, is generally safe but can cause low potassium levels, high blood pressure, fluid retention, heart issues, and liver problems. These side effects were mostly mild to moderate in clinical trials. ^{2 3 4 6 7}

What makes the drug abiraterone acetate unique for treating metastatic castration-resistant prostate cancer?

Abiraterone acetate (Zytiga) is unique because it is an oral medication that selectively inhibits the cytochrome P450 17A1 enzyme, which is crucial for testosterone production, and is used in combination with prednisone to improve survival in patients with metastatic castration-resistant prostate cancer who have previously received chemotherapy. ^{1 2 3 4 6}

Research Team

Jingsong Zhang, MD

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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®) 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, 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]

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]

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]

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]

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]

References

1. Sweden 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. [2017]

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

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021]

3. United States 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. [2018]

4. Germany 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. [2022]

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

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

6. Netherlands pubmed.ncbi.nlm.nih.gov

Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate. [2020]

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

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