ChemoHormonal Therapy for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: OHSU Knight Cancer Institute

Must be taking: Apalutamide, Abiraterone, Prednisone

Must not be taking: Atypical antipsychotics, Tricyclic antidepressants

Disqualifiers: Seizure, Uncontrolled hypertension, Active infection, 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: Unknown

Duration: 12 months

7 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well the combination of apalutamide, abiraterone acetate, and prednisone after chemotherapy work in treating patients that have received no prior treatment (treatment naive) for high risk prostate cancer that is sensitive to androgen deprivation therapy (castration sensitive) and has spread to other parts of the body (metastatic). This study also aims to understand the inheritance of prostate cancer. If a gene or genes that cause prostate cancer can be found, the diagnosis and treatment of prostate cancer may be improved. Testosterone (a male hormone) can cause the growth of prostate cancer cells. Hormone therapy using apalutamide may fight prostate cancer by blocking the use of testosterone by the tumor cells. Antihormone therapy, such as abiraterone acetate, may lessen the amount of testosterone made by the body. Anti-inflammatory drugs such as prednisone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Apalutamide, abiraterone acetate, and prednisone after chemotherapy may work better in treating patients with castration sensitive prostate cancer.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, medications that lower the seizure threshold and certain psychiatric medications must be stopped or substituted at least 4 weeks before starting the study. Additionally, some herbal agents and specific drugs like first-generation androgen receptor antagonists must be stopped before the trial begins.

What data supports the effectiveness of the drug combination used in the ChemoHormonal Therapy for Prostate Cancer trial?

Research shows that Apalutamide, when added to standard therapy, significantly improves survival and delays the need for chemotherapy in prostate cancer patients. Similarly, Abiraterone Acetate, combined with prednisone, has been proven to extend survival and delay disease progression in patients with advanced prostate cancer. ^{1 2 3 4 5}

Is ChemoHormonal Therapy for Prostate Cancer safe for humans?

Abiraterone acetate, used in combination with prednisone, is generally considered safe for treating prostate cancer, but it can cause side effects like low potassium levels, high blood pressure, fluid retention, and liver issues. These side effects were relatively low in frequency in clinical trials, but it's important to monitor for them during treatment. ^{2 3 6 7 8}

How is the drug combination of Abiraterone Acetate and Apalutamide unique for treating prostate cancer?

The combination of Abiraterone Acetate and Apalutamide is unique because Abiraterone Acetate works by blocking a specific enzyme (CYP17) to reduce androgen production, which is crucial for prostate cancer growth, while Apalutamide blocks androgen receptors, preventing cancer cells from using androgens. This dual approach targets prostate cancer more comprehensively than treatments using only one of these mechanisms. ^{2 4 6 7 9}

Research Team

Julie Graff, MD

Principal Investigator

OHSU Knight Cancer Institute

Eligibility Criteria

Men with high-risk, treatment-naive metastatic prostate cancer that is sensitive to hormone therapy are eligible. They must have completed up to 6 cycles of docetaxel chemotherapy and meet specific criteria including a PSA > 50 ng/mL, certain levels of disease spread, and no prior second-generation antiandrogen therapies. Participants need good organ function, controlled blood pressure without certain medications, no active infections like HIV or hepatitis, and agree to use contraception.

Inclusion Criteria

I have more than 4 bone lesions, with at least one outside my spine or pelvis, or I have cancer that has spread to my organs.

I can take care of myself but might not be able to do heavy physical work.

Patients must have a condition that is considered to be high risk for the study.

Exclusion Criteria

I am not taking specific drugs that don't mix well with the trial medication.

I have had a seizure or a condition that could lead to seizures, like a recent stroke.

I am willing to stop taking saw palmetto or other similar herbal supplements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive apalutamide, abiraterone acetate, and prednisone orally once daily, with cycles repeating every 4 weeks in the absence of disease progression or unacceptable toxicity. Androgen deprivation therapy is also administered per standard of care.

12 months

Monthly visits for treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 6 months for up to 10 years.

Up to 10 years

Biannual visits

Treatment Details

Interventions

• Abiraterone Acetate
• Apalutamide
• Prednisone

Trial Overview The trial tests the effectiveness of combining apalutamide, abiraterone acetate, and prednisone after chemotherapy in men with advanced prostate cancer. It also investigates genetic factors related to prostate cancer inheritance. The goal is to see if this combination works better for those who haven't had previous treatments and whose cancer still responds to hormone therapy.

Participant Groups

Group I: Treatment (apalutamide, abiraterone acetate, prednisone, ADT) Experimental Treatment 8 Interventions

Patients receive apalutamide PO QD, abiraterone acetate PO QD, and prednisone PO QD. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive androgen deprivation therapy per standard of care. Patients undergo CT scan, bone scan and blood sample collection throughout the study.

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?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Ricardo Attar

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology, University of Buenos Aires

Dr. Anastasia G. Daifotis

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2023

MD

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Findings from Research

In a phase III study (TITAN) involving men with metastatic castration-sensitive prostate cancer, adding apalutamide to androgen deprivation therapy significantly improved median radiographic progression-free survival and overall survival.

Apalutamide was found to maintain health-related quality of life and had a safety profile similar to that of placebo when combined with androgen deprivation therapy, expanding treatment options for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. Hoy, SM.[2021]

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]

In a study of 12 men with metastatic castrate-resistant prostate cancer (mCRPC) who were re-treated with abiraterone acetate (AA), only 46% of those who initially responded to AA showed a similar response upon re-treatment, indicating limited efficacy.

The median duration of response to AA re-treatment was short, with a median biochemical progression-free survival of just 2.3 months, suggesting that re-challenging with AA may not provide significant long-term benefits for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retreatment of men with metastatic castrate-resistant prostate cancer with abiraterone. Leibowitz-Amit, R., Alimohamed, N., Vera-Badillo, FE., et al.[2016]

Abiraterone acetate is the first second-line hormonal treatment shown to improve survival in metastatic castration-resistant prostate cancer, initially approved in 2011 for patients who had not responded to docetaxel, showing a 4-month survival benefit.

The FDA has expanded its use to the pre-chemotherapy setting due to significant delays in disease progression and trends toward increased overall survival, with ongoing studies investigating its effectiveness in earlier stages and in combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: targeting persistent androgen dependence in castration-resistant prostate cancer. Harshman, LC., Taplin, ME.[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 (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]

Men with advanced prostate cancer taking abiraterone have a significantly higher risk of major metabolic or cardiovascular adverse events compared to those not on the medication, with a hazard ratio of 1.77.

Enzalutamide also increases the risk of major adverse events, but to a lesser extent (hazard ratio of 1.22), and does not significantly increase the risk of minor adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer. Lai, LY., Oerline, MK., Caram, MEV., et al.[2023]

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]

References

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

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. [2021]

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

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

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

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

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

Retreatment of men with metastatic castrate-resistant prostate cancer with abiraterone. [2016]

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

Abiraterone acetate: targeting persistent androgen dependence in castration-resistant prostate cancer. [2021]

6. 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]

7. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer. [2023]

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

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