Androgen Receptor Therapies for Prostate Cancer

Not currently recruiting at 4 trial locations

Overseen By Study Coordinator

Age: 18+

Sex: Male

Trial Phase: Phase 4

Sponsor: Northwestern University

Must be taking: GnRH agonists, GnRH antagonists

Must not be taking: Psychotropic medications, Illicit drugs

Disqualifiers: Cognitive impairment, Seizure history, Uncontrolled illness, 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: 4

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how treatments for prostate cancer, specifically androgen receptor therapies like abiraterone acetate (Zytiga) and enzalutamide (Xtandi), might affect cognitive function. Researchers use MRI scans to determine if these treatments alter brain structure or activity and seek genetic differences that might increase sensitivity to these changes. Men treated for prostate cancer with specific hormone therapies who can complete surveys in English might be suitable for this study. As a Phase 4 trial, this research aims to understand how these FDA-approved treatments can benefit more patients.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking psychotropic medications or illicit drugs that may affect cognition, unless they are stable doses of certain medications for depression or anxiety.

What is the safety track record for these treatments?

Research shows that both abiraterone acetate and enzalutamide are generally safe for treating prostate cancer, though they can cause some side effects. Studies found serious side effects in about 64.1% of patients taking abiraterone, compared to 71.8% on standard treatment. Abiraterone has helped many patients live longer.

Enzalutamide also shows promising results. One study found it reduced the risk of death by 33% compared to a control group. Another study demonstrated that patients taking enzalutamide lived longer overall than those on other treatments.

Both treatments have FDA approval for prostate cancer, indicating they have passed strict safety tests. While some serious side effects have been reported, these treatments are generally well-tolerated. Discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for prostate cancer because they target the androgen receptor pathway, which plays a crucial role in the disease's progression. Unlike traditional therapies that only manage symptoms, Abiraterone Acetate and Enzalutamide work by blocking the effects of male hormones that fuel cancer growth. Abiraterone Acetate is taken with prednisone and inhibits the production of androgens, while Enzalutamide blocks the androgen receptors more directly. These approaches offer a more targeted mechanism, potentially leading to better management of the disease with fewer side effects compared to conventional treatments.

What is the effectiveness track record for androgen receptor therapies in treating prostate cancer?

Research has shown that both abiraterone acetate and enzalutamide effectively treat prostate cancer. In this trial, participants in one arm will receive abiraterone acetate with prednisone. Studies have found that this combination can extend life, regardless of prior chemotherapy. Nearly all clinical trials for abiraterone have succeeded, with 89% achieving their goals. Participants in another arm will receive enzalutamide, which has also significantly improved survival rates. For instance, one study showed a survival rate of 50% compared to 40% with other treatments, and it also slowed tumor growth. Both treatments have strong evidence of extending life for prostate cancer patients. ^{3 4 5 6 7}

Who Is on the Research Team?

David VanderWeele, M.D., M.P.H.

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

Men with advanced prostate cancer who can take oral meds, complete English surveys without help, and have either newly diagnosed metastatic hormone sensitive or castration-resistant prostate cancer. They must be willing to sign consent in English, may have had certain prior treatments but not extensive chemotherapy or brain radiation, and should be over 18 years old.

Inclusion Criteria

Patients must be able to take oral medication

Willing and able to complete survey questionnaires in English without assistance through the duration of the study. This stipulation is in place because not all of the proposed quality of life or cognitive tests are available or validated in other languages

Have either newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) or castration-resistant metastatic prostate cancer (mCRPC) and eligible to undergo treatment with abiraterone acetate (mHSPC or mCRPC) or enzalutamide (mCRPC)

Exclusion Criteria

Uncontrolled intercurrent illness including, but not limited to, uncontrolled diabetes, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III and IV heart failure), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations/substance abuse that would limit compliance with study requirements

Patients with a 'currently active' second malignancy other than non-melanoma skin cancers are not eligible. Patients are not considered to have a 'currently active' malignancy if they have completed all therapy and are now considered without evidence of disease for 1 year. Patients with cognitive dysfunction related to treatment of another malignancy, including a history of 'chemo-brain', are ineligible

Patients taking psychotropic medications or illicit drugs that may alter cognition, concentration, or behavior. Appropriate treatment by a licensed provider with medications for depression or anxiety, including but not limited to SSRIs, SNRIs, and standard dose benzodiazepines at a stable dose, is permitted

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive androgen receptor directed therapies such as abiraterone acetate and enzalutamide, with cognitive assessments and MRI imaging at baseline, 3, 6, and 12 months

12 months

4 visits (in-person) at baseline, 3, 6, and 12 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
• Enzalutamide
• GnRH agonist/antagonist
• Prednisone

Trial Overview

The trial is studying the impact of androgen receptor directed therapies like abiraterone acetate and enzalutamide on cognitive function using MRI scans. It also looks for genetic factors that might influence sensitivity to cognitive changes during treatment.

How Is the Trial Designed?

Group I: Arm II (enzalutamide) Experimental Treatment 2 Interventions

Patients receive standard of care treatment with GnRH agonist/antagonist therapy. Patients also receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo cognitive assessment and MRI program as in Arm I.

Group II: Arm I (abiraterone acetate, prednisone) Experimental Treatment 3 Interventions

Patients receive standard of care treatment with GnRH agonist/antagonist therapy. Patients also receive abiraterone acetate PO and prednisone PO BID in the absence of disease progression or unacceptable toxicity. Patients then undergo cognitive assessment comprising of neuro-cognitive tests and assessments of overall quality of life, fatigue, pain, and symptoms at baseline, 3, 6, and 12 months. Patients also undergo MRI program for 40 minutes comprising of DTI, fMRI, ASL MRI, MPRAGE MRI, FLAIR MRI, and BOLD MRI at baseline and 3 months.

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?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8105236/

Real-World Safety and Efficacy Outcomes with Abiraterone ...

Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients.

2.

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.

3.

nature.com

nature.com/articles/s41391-024-00816-0

Real-world overall survival with abiraterone acetate versus ...

There are no large head-to-head phase 3 clinical trials comparing overall survival (OS) for abiraterone and enzalutamide.

4.

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. Our ...

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 ...

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 ...

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 ...