Abiraterone + Antiandrogen +/- Chemotherapy for Advanced Prostate Cancer

Not currently recruiting at 694 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: ECOG-ACRIN Cancer Research Group

Must be taking: Androgen deprivation

Must not be taking: Antibiotics, Corticosteroids

Disqualifiers: Active infection, Heart failure, 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: 9

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment options for advanced prostate cancer that resists standard hormone therapy. It examines whether combining hormone therapy (antiandrogen therapy) with chemotherapy can more effectively stop the cancer from growing and spreading. Participants will be divided into groups to receive different combinations of hormone therapy and chemotherapy. Men whose prostate cancer has spread, who have previously been treated with docetaxel, and who continue to see cancer progression despite standard hormone treatment might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial requires that you continue your current androgen deprivation treatment throughout the study. If you have been treated with certain antiandrogens like flutamide, bicalutamide, or nilutamide, you must stop them for a specific period before joining: 4 weeks for flutamide and 6 weeks for bicalutamide or nilutamide.

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

Research has shown that combining abiraterone acetate and prednisone with cabazitaxel may benefit patients with prostate cancer. Studies have found that this combination can extend life, particularly for those who have previously tried treatments like docetaxel. Importantly, the side effects of these drugs are generally manageable.

For instance, one study found that using abiraterone acetate, prednisone, and cabazitaxel together was safe, with some patients experiencing common but manageable side effects such as tiredness, low blood cell counts, and digestive issues. Similarly, abiraterone acetate alone has been used in men with advanced prostate cancer, with the most serious side effects being high blood pressure and changes in liver function, which can be managed with proper medical care.

Overall, these treatments have been well-tolerated by previous patients, allowing most to handle the side effects without major problems. This suggests a level of safety that could reassure those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for advanced prostate cancer because they combine abiraterone acetate with antiandrogen therapy and possibly chemotherapy, offering a potentially more comprehensive approach. Unlike standard treatments that typically focus on either hormone therapy or chemotherapy alone, this approach uses abiraterone acetate to block androgen production more effectively when paired with either LHRH agonists or surgical castration. The addition of cabazitaxel in one arm targets cancer cells directly, potentially enhancing the treatment's effectiveness against aggressive cancer cells. This multi-pronged strategy could offer improved outcomes for patients with advanced prostate cancer by tackling the disease from several angles simultaneously.

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

In this trial, participants will receive different treatment combinations for advanced prostate cancer. Research has shown that combining abiraterone acetate, cabazitaxel, and prednisone can effectively treat advanced prostate cancer. Specifically, participants in Arm A will receive abiraterone acetate with prednisone and cabazitaxel, which has been linked to improved survival rates and slowed cancer progression. One study found that using abiraterone acetate with prednisone was associated with a 43% decrease in the chance of cancer worsening. Adding cabazitaxel further improved results, especially for those whose cancer did not respond to previous treatments. These findings suggest that this treatment approach might control cancer growth better than some other options. Meanwhile, participants in Arm B will receive abiraterone acetate and prednisone without cabazitaxel. ^{1 6 7 8 9}

Who Is on the Research Team?

Christos Kyriakopoulos

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

Men with metastatic, castration-resistant prostate cancer previously treated with docetaxel can join. They must have low testosterone levels, adequate organ function, and no active infections or recent heart issues. Participants need to be on standard hormone therapy and not taking other investigational drugs. Men who've had certain treatments like radium-223 are allowed.

Inclusion Criteria

I may have been treated with a specific hormone therapy before.

Creatinine < 2.0 mg/dL

Informed consent form signed

Exclusion Criteria

ALT or AST aminotransferase > 1.5 x ULN

I have received chemotherapy or therapy targeting the androgen receptor for prostate cancer.

My prostate cancer is not the common type but a rare form.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abiraterone acetate and prednisone, with or without cabazitaxel, for up to 6 cycles of 21 days each

18 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 3 or 6 months, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone Acetate
• Antiandrogen Therapy
• Cabazitaxel
• Prednisone

Trial Overview The trial is testing if adding cabazitaxel and prednisone to abiraterone acetate and antiandrogen therapy improves outcomes in patients whose prostate cancer has spread despite treatment. It's a randomized study comparing the effectiveness of these combinations after previous chemotherapy.

How Is the Trial Designed?

Group I: Arm A (abiraterone acetate, prednisone, cabazitaxel) Experimental Treatment 7 Interventions

Patients receive abiraterone acetate PO QD on days 1-21, prednisone PO BID on days 1-21. Courses of abiraterone acetate and prednisone repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients receive cabazitaxel IV over 1 hour on day 1, and treatment with cabazitaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.

Group II: Arm B (abiraterone acetate, prednisone) Active Control 6 Interventions

Patients receive abiraterone acetate and prednisone as in Arm A. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.

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?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

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]

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 phase II study involving 41 men with metastatic castration-resistant prostate cancer, increasing the dose of abiraterone acetate from 1000 mg to 2000 mg daily did not result in any significant clinical benefit, as no patients showed a prostate-specific antigen (PSA) decline of 30% or more after 12 weeks.

The study found that factors such as lower baseline circulating androgen levels and individual differences in drug metabolism may contribute to resistance against standard-dose abiraterone therapy, suggesting that simply increasing the dose is not an effective strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Abiraterone Acetate in Men With Castration Resistant Prostate Cancer. Friedlander, TW., Graff, JN., Zejnullahu, K., et al.[2018]

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]

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]

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]

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]

Citations

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2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6683519/

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Randomized Phase II Multicenter Trial of Abiraterone ... Preclinical studies showed cabazitaxel had superior antitumor efficacy compared with docetaxel. Gene expression profiling revealed divergent ...

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Cabazitaxel versus Abiraterone or Enzalutamide in ... Cabazitaxel significantly improved a number of clinical outcomes, as compared with the androgen-signaling–targeted inhibitor (abiraterone or enzalutamide),

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Final efficacy and safety analysis of the CAPRO study. Background: Abiraterone acetate + prednisone (AA) and cabazitaxel (CB) have shown an improvement in overall survival after Docetaxel (DOC) in (mCRPC)1,2.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0302283821018625

Efficacy and Safety of Cabazitaxel Versus Abiraterone or ... Clinical trial data showed that cabazitaxel improved survival versus abiraterone/enzalutamide with manageable side effects in patients with metastatic ...

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Abiraterone for Prostate Cancer Not Previously Treated ... Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer. We assessed the effect of this combination in men starting long- ...