Hormone Therapy + Medications for Prostate Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining hormone therapy, surgery, and possibly radiation can effectively shrink prostate cancer and reduce its recurrence. It includes medications that lower male hormone levels for a few months before surgery, such as a GnRH agonist/antagonist (a type of hormone therapy). Men with aggressive prostate cancer or newly diagnosed low-volume metastatic disease, who haven't undergone extensive prior treatment, might be suitable candidates. The goal is to determine if this approach can make prostate-specific antigen (PSA) levels undetectable, indicating that the cancer is under control. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that the medications used in this trial are generally well-tolerated by patients. Studies have found apalutamide to be safe and effective in both clinical trials and everyday use. In one study, only 0.2% of patients taking apalutamide experienced serious side effects, such as problems with blood flow in the brain. Another study combined apalutamide with stereotactic body radiotherapy (SBRT) and found that only 2.2% of patients had severe side effects.

When apalutamide is used with other treatments like hormone therapy (ADT), abiraterone acetate, and prednisone, research shows this combination is generally safe and well-tolerated. One analysis found that this combination significantly improved patient outcomes with manageable side effects.

These findings suggest that the treatments in this trial have a good safety record. However, it is important to discuss any concerns with the trial team, as individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they offer innovative approaches that differ from traditional methods. Unlike standard treatments, which typically involve surgery or chemotherapy, these investigational therapies combine hormone therapy with advanced medications like Apalutamide and Abiraterone Acetate. Apalutamide works by blocking the effects of androgens, which are hormones that can promote prostate cancer growth. Additionally, the combination of androgen deprivation therapy (ADT) with targeted medications aims to enhance treatment effectiveness and potentially improve outcomes. This multi-faceted approach could lead to more effective management of prostate cancer, providing hope for patients seeking alternatives to conventional therapies.

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

Research shows that combining hormone therapy drugs like apalutamide with surgery and possibly radiation can help manage aggressive prostate cancer. In this trial, participants may receive apalutamide with androgen deprivation therapy (ADT), which studies have shown reduces the risk of death by 23% over two years compared to another treatment. Another arm of this trial adds the drugs abiraterone acetate and prednisone to ADT, which has been reported to improve cancer outcomes after surgery. Additionally, using apalutamide with a precise form of radiation therapy (stereotactic body radiotherapy or SBRT) and regular radiation therapy is another treatment option being tested. Studies have shown that 71% of patients experienced no cancer progression after three years with this approach. These treatments work by reducing male hormones that help the cancer grow, aiming to shrink the tumor and lower PSA levels, which are markers of prostate cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Matthew Dallos, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9377412/

Apalutamide plus abiraterone acetate and prednisone in ... The addition of apalutamide to abiraterone-prednisone versus abiraterone-prednisone alone resulted in a significantly higher rate of confirmed ≥ ...

2. targetedonc.com targetedonc.com/view/abiraterone-prednisone-apalutamide-improves-prostate-cancer-outcomes-leaves-hrqol-unaffected

Abiraterone, Prednisone, Apalutamide Improves Prostate ... Oncological outcomes improved with the addition of abiraterone acetate (Zytiga) plus prednisone (AAP) and apalutamide (Erleada) after radical prostatectomy.

3. nature.com nature.com/articles/s41391-024-00929-6

Survival outcomes of apalutamide as a starting treatment First-line APA + ADT in mHSPC was associated with statistically significantly longer OS, longer TTCR, and faster and deeper PSA responses than other life- ...

4. becarispublishing.com becarispublishing.com/doi/10.57264/cer-2025-0023

a head-to-head analysis of real-world patients in the USA The results of this study show that compared with abiraterone acetate, initial treatment with apalutamide resulted in better real-world survival ...

5. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1656216/full

Efficacy and safety of apalutamide, abiraterone acetate ... Results: This study analyzed 146 mHSPC patients. The results are displayed that Apalutamide and Abiraterone significantly prolonged PFS and PSA- ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12554570/

Efficacy and safety of apalutamide, abiraterone acetate ... This study analyzed 146 mHSPC patients. The results are displayed that Apalutamide and Abiraterone significantly prolonged PFS and PSA-PFS ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03360721

NCT03360721 | Apalutamide, Abiraterone Acetate, and ... Giving apalutamide, abiraterone acetate, and prednisone may work better in treating participants with castration resistant prostate cancer. Detailed Description.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10191952/

A Phase I Clinical Trial Evaluating the Safety and Dosing of ... In this interim analysis, combination treatment with relugolix and abiraterone or apalutamide was generally safe and well tolerated in patients with advanced ...

9. thelancet.com thelancet.com/article/S0140-6736(21)02437-5/fulltext

Abiraterone acetate and prednisolone with or without ... Our results suggest a clear improvement in metastasis-free and overall survival from the addition of 2 years of abiraterone to ADT in men with ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT02867020?term=APALUTAMIDE&rank=1

Study of Abiraterone Acetate Plus ADT Versus ... Evaluation of the activity, safety and patients reported outcome of ADT plus abiraterone, abiraterone plus APALUTAMIDE (a second-generation antiandrogen) or ...