Anti-androgen Treatment for Prostate Cancer

Age: Any Age

Sex: Male

Trial Phase: Academic

Sponsor: Ohio State University Comprehensive Cancer Center

Must be taking: Anti-androgens

Disqualifiers: Active malignancy, Cardiovascular disease, others

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 4-7 months

23 Participants Needed

Trial Summary

What is the purpose of this trial?

Learning about the impact of anti-androgen treatment has on cardiac function in patients with prostate cancer may help plan treatment and help patients live more comfortably. This pilot clinical trial will utilize cardiac magnetic resonance imaging (MRI) before a patient starts hormone therapy and after 4 to 7 months of hormone therapy. The objective is to measure the impact of hormone therapy (anti-androgen treatment) on cardiac function in patients with prostate cancer.

Do I need to stop taking my current medications for this trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment for prostate cancer?

Hormonal therapy, which includes treatments like anti-androgens, is designed to block androgens (male hormones) that help prostate cancer cells grow. Research shows that hormonal therapy can be effective in prolonging survival, especially when used early in the treatment of prostate cancer, and it is considered a standard treatment for advanced cases. ^{1 2 3 4 5}

Is anti-androgen treatment for prostate cancer safe for humans?

The safety of anti-androgen treatments like letrozole, anastrozole, and exemestane has been studied in breast cancer patients. These treatments are generally well tolerated, but letrozole may increase the risk of bone fractures and heart issues, while tamoxifen may increase the risk of uterine cancer and blood clots. ^{6 7 8 9 10}

How is anti-androgen treatment for prostate cancer different from other treatments?

Anti-androgen treatment for prostate cancer is unique because it targets the androgen receptor, which is crucial for the growth of prostate cancer cells, and can be effective even in cases where the cancer is resistant to traditional hormone therapy. This approach can improve survival and quality of life by using drugs like abiraterone acetate and enzalutamide, which are designed to lower testosterone levels or block its effects. ^{11 12 13 14 15}

Research Team

Steven Clinton, MD, PhD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for men with prostate cancer who are about to start at least 4 months of hormone therapy. They should be in good physical condition (ECOG status 0-1), have cholesterol and triglycerides levels below 200 mg/dL, normal kidney and liver function tests, a complete blood count within the normal range, and no significant clotting disorders.

Inclusion Criteria

Have plasma triglycerides < 200 mg/dL

I have been diagnosed with prostate cancer through a biopsy.

I am about to start a specific hormone therapy for at least 4 months.

Exclusion Criteria

I have no heart-related reasons preventing me from doing exercise tests.

I am being treated for a cancer other than prostate cancer.

I have a heart condition or severe illness that makes moderate exercise unsafe.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo a treadmill stress CMR and skeletal muscle PMRS before initiation of ADT treatment

1 day

1 visit (in-person)

Treatment

Participants receive anti-androgen treatment (ADT) for 4-7 months

4-7 months

Post-Treatment Assessment

Participants undergo a treadmill stress CMR and skeletal muscle PMRS 4-7 months after initiation of ADT treatment

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Hormone Therapy

Trial Overview The study uses cardiac MRI to assess how anti-androgen treatments affect heart function in prostate cancer patients. Participants will undergo MRIs before starting hormone therapy and after 4 to 7 months on treatment to monitor changes in their cardiac health.

Participant Groups

Group I: Diagnostic (cardiac MRI, skeletal muscle PMRS) Experimental Treatment 5 Interventions

Patients undergo a treadmill stress CMR focused on cardiac muscle comprised of resting MRI over 10-15 minutes followed by treadmill exercise until peak stress. Patients then undergo MRI and gadopentetate dimeglumine perfusion imaging immediately after exercise and after a 6-8 minute recovery period. Within 24 hours of treadmill CMR exam, patients also undergo skeletal muscle PMRS while at rest, during, and in the recovery phase of resistive lower extremity exercise which patients complete over 30 seconds. Both procedures are performed before initiation of ADT treatment (baseline) and 4-7 months after initiation of ADT treatment.

Hormone Therapy is already approved in European Union, United States, Canada, Japan, Switzerland for the following indications:

Approved in European Union as Hormone Therapy for:

• Breast cancer
• Hormone receptor-positive breast cancer

Approved in United States as Hormone Therapy for:

• Breast cancer
• Hormone receptor-positive breast cancer
• Stage I-III breast cancer

Approved in Canada as Hormone Therapy for:

• Breast cancer
• Hormone receptor-positive breast cancer

Approved in Japan as Hormone Therapy for:

• Breast cancer
• Hormone receptor-positive breast cancer

Approved in Switzerland as Hormone Therapy for:

• Breast cancer
• Hormone receptor-positive breast cancer

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

Pelontonia

Collaborator

Trials

1

Recruited

20+

Findings from Research

Hormonal treatment for prostate cancer aims to reduce androgen levels, and various methods like orchiectomy and medications can achieve this effectively, with all methods showing similar efficacy.

While orchiectomy is a safe procedure, it may have psychological effects, and other treatments like estrogens and synthetic hormone analogs have their own risks, making patient preference and side effects important factors in treatment selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hormonal therapy of prostate cancer: current concepts and future prospects. Smith, JA.[2005]

Letrozole, an aromatase inhibitor, has been shown to be significantly more effective than tamoxifen in treating advanced breast cancer, particularly in terms of median time to progression and response rates, while being well tolerated by patients.

Anastrozole and exemestane also provide effective alternatives to tamoxifen, with anastrozole showing equivalent efficacy overall but superior results in hormone receptor-positive patients, and exemestane demonstrating better response rates, although overall survival data is still pending.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors in advanced breast cancer. Mouridsen, HT.[2019]

Letrozole, a third-generation aromatase inhibitor, effectively lowers estrogen levels in postmenopausal women and has been shown to be more effective than tamoxifen in treating hormone-receptor-positive early breast cancer.

Clinical trials indicate that letrozole significantly improves disease-free survival, particularly in high-risk patients, making it a crucial option in adjuvant therapy for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on the use of letrozole in breast cancer. Wu, M., Goss, PE.[2019]

Letrozole has been fully approved by the FDA for treating postmenopausal women with hormone receptor-positive early breast cancer, showing a significant improvement in disease-free survival compared to tamoxifen, with a hazard ratio of 0.87 in the adjuvant trial.

While letrozole is effective, it is associated with a higher risk of bone fractures and myocardial infarction compared to tamoxifen, which has its own risks such as endometrial cancer and thromboembolic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approval summary: letrozole (Femara® tablets) for adjuvant and extended adjuvant postmenopausal breast cancer treatment: conversion of accelerated to full approval. Cohen, MH., Johnson, JR., Justice, R., et al.[2021]

In a study of 40 postmenopausal women with locally advanced breast cancer, both Letrozole and Tamoxifen were found to be effective as neoadjuvant hormone therapies, with 25% of patients on Tamoxifen and 20% on Letrozole not achieving a complete response, leading to subsequent radiotherapy.

The study indicated that neoadjuvant hormone therapy was generally well-tolerated, with side effects occurring in 55% of patients on Letrozole and 60% on Tamoxifen, suggesting that these treatments could improve clinical outcomes and allow for successful radical mastectomy in patients with better prognoses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Letrozole vs. tamoxifen as neoadjuvant therapy for postmenopausal patients with hormone-dependent locally-advanced breast cancer]. Novoa Vargas, A., Font López, KC., Amador, DD.[2018]

Anastrozole and letrozole significantly improve disease-free survival compared to tamoxifen in postmenopausal women with early-stage breast cancer, based on results from Phase III trials.

Switching to an aromatase inhibitor like anastrozole or exemestane after 2 to 3 years of tamoxifen therapy reduces the risk of cancer recurrence more effectively than continuing tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are all aromatase inhibitors the same? A review of controlled clinical trials in breast cancer. Berry, J.[2007]

Abiraterone acetate combined with prednisone significantly improves overall survival (34.7 months vs 30.3 months) and radiologic progression-free survival (16.5 months vs 8.3 months) in patients with metastatic castration-resistant prostate cancer compared to placebo.

The treatment is generally well-tolerated, with manageable side effects primarily related to mineral corticoid excess, and it also enhances the perceived quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Abiraterone in castration resistant prostate cancer.] Juárez Soto, A., Caballero Cobos, R., Campanario Pérez, R., et al.[2018]

References

1. France pubmed.ncbi.nlm.nih.gov

[Cancer of the prostate: new hormone therapies]. [2013]

2. France pubmed.ncbi.nlm.nih.gov

[Prognostic factors of prostate cancer treated with first-line hormone therapy]. [2015]

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

Hormonal therapy of prostate cancer: current concepts and future prospects. [2005]

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

Early versus late hormonal therapy: debating the issues. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Prognostic significance of changes in short-term prostate volume and serum prostate-specific antigen after androgen withdrawal in men with metastatic prostate cancer. [2017]

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

Aromatase inhibitors in advanced breast cancer. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Update on the use of letrozole in breast cancer. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Approval summary: letrozole (Femara® tablets) for adjuvant and extended adjuvant postmenopausal breast cancer treatment: conversion of accelerated to full approval. [2021]

9. Mexico pubmed.ncbi.nlm.nih.gov

[Letrozole vs. tamoxifen as neoadjuvant therapy for postmenopausal patients with hormone-dependent locally-advanced breast cancer]. [2018]

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

Are all aromatase inhibitors the same? A review of controlled clinical trials in breast cancer. [2007]

11. France pubmed.ncbi.nlm.nih.gov

[Hormonal treatment in prostate cancer]. [2021]

12. France pubmed.ncbi.nlm.nih.gov

[Therapeutic targeted approaches on androgen receptors in prostate cancer]. [2016]

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

Timing hormonal therapy in prostate cancer. [2019]

14. Spain pubmed.ncbi.nlm.nih.gov

[Abiraterone in castration resistant prostate cancer.] [2018]

15. Canada pubmed.ncbi.nlm.nih.gov

Secondary hormonal manipulations in the management of advanced prostate cancer. [2013]