Hormone Therapy + Medications for Prostate Cancer

Recruiting at 13 trial locations

Overseen By James Eastham, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Hormone therapy

Must not be taking: Antidepressants, Antivirals

Disqualifiers: Prior chemotherapy, Brain metastasis, 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

102 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test if treatment with medications that reduce the male hormone level in the participant's body for a few months before surgery can shrink prostate cancer as much as possible, which might reduce the chances of the cancer coming back in the future. These treatments include a hormone injection given monthly or every three months and the study drugs, which include abiraterone acetate, prednisone, and apalutamide. These medications are being used in combination with surgery and maybe radiotherapy because studies have shown that any single approach on its own is not sufficient to control or get rid of the cancer especially if they have high risk or aggressive features. The researchers hope to learn if combining the study drugs with surgery and radiation will get rid of the cancer from participants' prostates and reduce their prostate-specific antigen (PSA) to an undetectable level.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that certain medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks before starting the treatment. It's best to discuss your current medications with the trial team to ensure compatibility.

What data supports the effectiveness of GnRH antagonists in the treatment of prostate cancer?

Research shows that GnRH antagonists are effective in rapidly reducing testosterone levels, which helps in managing prostate cancer. They are at least as effective as GnRH agonists in terms of controlling cancer progression and are particularly beneficial for patients with cardiovascular issues. ^{1 2 3 4 5}

Is hormone therapy for prostate cancer safe for the heart?

Hormone therapies like GnRH agonists and antagonists, used for prostate cancer, can increase the risk of heart-related problems. Some studies suggest that GnRH antagonists might have a lower risk of these heart issues compared to GnRH agonists. ^{2 6 7 8 9}

How is the hormone therapy with GnRH agonist/antagonist and radical prostatectomy unique for prostate cancer?

This treatment combines hormone therapy with GnRH agonists or antagonists, which rapidly reduce testosterone levels, with radical prostatectomy, a surgical procedure to remove the prostate. The unique aspect is the combination of rapid testosterone suppression with surgery, potentially offering better cancer control for high-risk prostate cancer patients. ^{1 2 5 8 10}

Research Team

Matthew Dallos, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Men over 18 with advanced prostate cancer, who can consent and have adequate organ function. They must not have other active cancers or major health issues that could interfere with the trial, no prior treatments for prostate cancer (with some exceptions), and agree to use effective contraception.

Inclusion Criteria

My liver, kidneys, and bone marrow are functioning well.

My primary tumor cannot be surgically removed.

I can swallow pills without any difficulty.

Exclusion Criteria

Human immunodeficiency virus (HIV)-positive subjects with specific criteria

Concomitant therapy with any other experimental drug

Significant medical condition other than cancer that would prevent consistent and compliant participation in the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Hormone Treatment

Participants receive hormone injections and study drugs (abiraterone acetate, prednisone, and apalutamide) to reduce male hormone levels before surgery

3-6 months

Surgery

Participants undergo surgery to remove prostate cancer

1 week

Radiation

Participants may receive radiotherapy to further treat prostate cancer

4-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including PSA levels

24 months

Treatment Details

Interventions

• Abiraterone Acetate
• Apalutamide
• Extended Pelvic lymphadenectomy
• GnRH agonist/antagonist
• Prednisone
• Radical Prostatectomy
• Stereotactic Body Radiation Therapy

Trial Overview The study tests if hormone reduction drugs before surgery can shrink prostate cancer effectively. It combines monthly hormone injections, abiraterone acetate, prednisone, apalutamide with surgery and possibly radiotherapy to see if this approach is more successful in eliminating cancer.

Participant Groups

Group I: Apalutamide, SBRT, Radiation Experimental Treatment 2 Interventions

Group II: ADT + Apalutamide + Abiraterone Acetate + Prednisone Experimental Treatment 6 Interventions

This arm is no longer being assigned to subjects.

Group III: ADT + Apalutamide Experimental Treatment 4 Interventions

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

Findings from Research

In a study of 117 hormone-sensitive prostate cancer patients, those treated with GnRH antagonists showed a significantly higher prostate-specific antigen (PSA) control rate (54.28% without abiraterone and 88% with abiraterone) compared to those treated with GnRH agonists (47.91% without and 72% with abiraterone).

Propensity score matching revealed that the PSA control rates were 84.38% for antagonists versus 53.13% for agonists, indicating that GnRH antagonists are more effective in controlling PSA levels and serve as an independent predictor of treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of GnRH Antagonists and Agonists in Patients with Hormone-Sensitive Prostate Cancer: A Retrospective Study. Liu, Z., Yang, C., Zeng, X., et al.[2023]

GnRH antagonists significantly reduce cardiovascular risk compared to LHRH agonists in patients undergoing androgen deprivation therapy for metastatic prostate cancer, with a hazard ratio of 0.597, indicating a 40% lower risk.

Patients with pre-existing cardiovascular conditions benefit even more, showing a 56% lower risk of cardiovascular events when treated with GnRH antagonists compared to LHRH agonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cardiovascular risk patients under androgen deprivation therapy: Lower risk with GnRH antagonists compared to LHRH agonists?]. Merseburger, AS., Sedding, D., Hüter, K.[2018]

In a study of 142 high-risk prostate cancer patients, six months of neoadjuvant therapy with LHRH agonist and low-dose estramustine phosphate (EMP) before radical prostatectomy resulted in a 4.9% rate of complete pathological response (pT0) and 87% of patients had negative surgical margins, indicating effective cancer control.

The treatment was well-tolerated with no serious adverse events reported, and at a median follow-up of 34.9 months, 84.3% of patients remained free of prostate-specific antigen (PSA) recurrence, suggesting promising efficacy and safety for this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of neoadjuvant luteinizing hormone-releasing hormone agonist plus low-dose estramustine phosphate in high-risk prostate cancer: a prospective single-arm study. Koie, T., Ohyama, C., Yamamoto, H., et al.[2013]

The PRONOUNCE trial is a significant study involving approximately 900 men with advanced prostate cancer and pre-existing cardiovascular disease, comparing the cardiovascular safety of the GnRH antagonist degarelix versus the GnRH agonist leuprolide over 12 months.

This study aims to determine if using a GnRH antagonist reduces the risk of major adverse cardiovascular events (MACEs) compared to a GnRH agonist, addressing concerns about increased cardiovascular risks associated with androgen deprivation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Safety of Degarelix Versus Leuprolide for Advanced Prostate Cancer: The PRONOUNCE Trial Study Design. Melloni, C., Slovin, SF., Blemings, A., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Current and emerging gonadotropin-releasing hormone (GnRH) antagonists for the treatment of prostate cancer. [2021]

2. Egypt pubmed.ncbi.nlm.nih.gov

Effectiveness of GnRH Antagonists and Agonists in Patients with Hormone-Sensitive Prostate Cancer: A Retrospective Study. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Efficacy of treatment with a GnRH antagonist in prostate cancer patients previously treated with a GnRH agonist. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Pharmacological treatment of patients with advanced prostate cancer. [2014]

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

Progress in Clinical Research on Gonadotropin-Releasing Hormone Receptor Antagonists for the Treatment of Prostate Cancer. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Cardiovascular adverse events-related to GnRH agonists and GnRH antagonists: analysis of real-life data from Eudra-Vigilance and Food and Drug Administration databases entries. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

[Cardiovascular risk patients under androgen deprivation therapy: Lower risk with GnRH antagonists compared to LHRH agonists?]. [2018]

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

Safety and effectiveness of neoadjuvant luteinizing hormone-releasing hormone agonist plus low-dose estramustine phosphate in high-risk prostate cancer: a prospective single-arm study. [2013]

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

Cardiovascular Safety of Degarelix Versus Leuprolide for Advanced Prostate Cancer: The PRONOUNCE Trial Study Design. [2022]

10. Poland pubmed.ncbi.nlm.nih.gov

The use of luteinizing hormone-releasing hormone analogues is still an indispensable element of therapy in castrate-resistant prostate cancer. [2023]