Hormone Therapy + Targeted Drugs for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must be taking: Hormone therapy

Must not be taking: Anticoagulants, Corticosteroids, Herbal products, others

Disqualifiers: Cardiovascular disease, Seizure history, Metastases, 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: 6-8 weeks

45 Participants Needed

Trial Summary

What is the purpose of this trial?

Prostate cancer is the most common cancer in men and the second leading cause of cancer death in men. The purpose of this research study is to compare prostate cancers treated with hormone therapy versus prostate cancers treated with hormone therapy plus drugs that directly target cancer cells.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does exclude those using certain medications like herbal products affecting prostate cancer, systemic corticosteroids above a certain dose, and medications affecting androgen levels or PSA. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug enzalutamide for prostate cancer?

Research shows that enzalutamide, when added to standard treatment, helps men with metastatic hormone-sensitive prostate cancer live longer and delays the progression of the disease compared to older treatments or a placebo. ^{1 2 3 4 5}

Is the hormone therapy with targeted drugs for prostate cancer safe?

Enzalutamide, one of the drugs used in this treatment, has been shown to be generally well-tolerated in clinical trials, although it can cause side effects like severe thrombocytopenia (low platelet count) and seizures in some cases. ^{5 6 7 8 9}

How is the drug combination of Degarelix and Enzalutamide unique for treating prostate cancer?

This drug combination is unique because Degarelix quickly reduces testosterone levels without causing an initial surge, while Enzalutamide blocks the androgen receptor to slow cancer growth, together offering a comprehensive approach to managing advanced prostate cancer. ^{7 10 11 12 13}

Research Team

Robert Reiter, M.D.

Principal Investigator

University of California, Los Angeles

Eligibility Criteria

Men over 18 with advanced prostate cancer who haven't had treatment for it yet can join this trial. They should be planning to have surgery, be in good health otherwise, and have a life expectancy of at least 6 months. Key requirements include normal organ function tests, no history of heart failure or arrhythmias, and they must use contraception.

Inclusion Criteria

I am diagnosed with prostate cancer and scheduled for surgery to remove it.

Willing and able to give informed consent

Willing to abstain from procreative sex or use contraception as required

Exclusion Criteria

I am not using any experimental drugs or herbal products that affect PSA levels.

I have brain metastasis or active leptomeningeal disease.

I have a history of seizures or conditions that could lead to seizures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hormone therapy with or without additional drugs targeting cancer cells

6-8 weeks

Weekly visits for monitoring and drug administration

Prostatectomy

Participants undergo prostatectomy to collect tissue for analysis

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dasatinib
• Degarelix
• Enzalutamide
• Trametinib

Trial Overview The study is testing if adding targeted cancer drugs (dasatinib or trametinib) to hormone therapy before surgery helps more than just hormone therapy alone. Men will get either the hormone drug degarelix plus enzalutamide or that combo with one of the other drugs.

Participant Groups

Group I: AR inhibition only Active Control 2 Interventions

AR inhibition only Group 1: degarelix + enzalutamide Endocrine therapy with degarelix and enzalutamide will continue for a minimum of 6 weeks and a maximum of 8 weeks in all groups prior to the planned prostatectomy.

Group II: AR inhibition plus MEK inhibition Active Control 3 Interventions

AR inhibition plus MEK inhibition Group 2: trametinib + degarelix + enzalutamide In Group 2, treatment with trametinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, trametinib will be administered for no less than two weeks and no more than four weeks.

Group III: AR inhibition plus SRC inhibition Active Control 3 Interventions

AR inhibition plus SRC inhibition Group 3: dasatinib + degarelix + enzalutamide In Group 3, treatment with dasatinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, dasatinib will be administered for no less than two weeks and no more than four weeks.

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

Approved in European Union as Firmagon for:

• Advanced hormone-dependent prostate cancer

Approved in United States as Firmagon for:

• Advanced prostate cancer

Approved in Canada as Firmagon for:

• Hormone-sensitive prostate cancer

Approved in Japan as Firmagon for:

• Prostate cancer

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Medivation, Inc.

Industry Sponsor

Trials

76

Recruited

11,200+

Dr. David Hung

Medivation, Inc.

Chief Executive Officer since 2003

MD from University of California, San Francisco; AB in Biology from Harvard College

Dr. Stephen M. Kelsey

Medivation, Inc.

Chief Medical Officer since 2013

MD from University of Birmingham

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Prostate Cancer Foundation

Collaborator

Trials

52

Recruited

3,000+

Astellas Pharma Inc

Industry Sponsor

Trials

700

Recruited

236,000+

Headquarters

Tokyo, Japan

Top Products

- Xtandi (enzalutamide) for prostate cancer, - Xospata (gilteritinib) for AML, - Padcev (enfortumab vedotin) for bladder cancer, - Prograf (tacrolimus) for organ rejection prevention

Tadaaki Taniguchi

Astellas Pharma Inc

Chief Medical Officer since 2023

MD, PhD

Naoki Okamura

Astellas Pharma Inc

Chief Executive Officer since 2023

University of Tokyo, Faculty of Pharmacy

Findings from Research

In men with metastatic hormone-sensitive prostate cancer, enzalutamide, when combined with androgen-deprivation therapy, significantly prolonged radiographic progression-free survival compared to a placebo.

This finding highlights the efficacy of enzalutamide as an androgen-receptor inhibitor in improving outcomes for patients undergoing treatment for advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eyeing Enzalutamide for Hormone-Sensitive Prostate Cancer. [2020]

In the ARCHES trial involving 1150 men with metastatic hormone-sensitive prostate cancer, enzalutamide combined with androgen deprivation therapy (ADT) significantly improved overall survival and radiographic progression-free survival in both men aged <75 and ≥75 years, although younger patients had better outcomes.

Despite older patients experiencing more treatment interruptions and adverse events, enzalutamide was generally well tolerated, indicating its effectiveness and safety for treating prostate cancer in older men.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes of Enzalutamide in Metastatic Hormone-sensitive Prostate Cancer in Patients Aged Gomez-Veiga, F., Szmulewitz, RZ., Holzbeierlein, J., et al.[2023]

The ENZAMET phase III trial demonstrated that adding enzalutamide to standard treatment significantly prolongs survival in men with metastatic hormone-sensitive prostate cancer.

Enzalutamide is more effective than older nonsteroidal antiandrogen drugs, highlighting its potential as a superior treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide Bests Older NSAAs in mHSPC. [2021]

Enzalutamide significantly improved radiographic progression-free survival (rPFS) in men with chemotherapy-naïve metastatic castration-resistant prostate cancer across various disease subgroups, including nonvisceral and visceral disease, as well as low- and high-volume bone disease.

The treatment was well tolerated, showing clinically significant benefits in overall survival (OS) for most subgroups, although the results were less definitive for patients with visceral disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer. Evans, CP., Higano, CS., Keane, T., et al.[2022]

A 76-year-old man developed severe thrombocytopenia after 13 days of enzalutamide treatment for castration-resistant prostate cancer, indicating that this side effect can occur early in therapy.

After discontinuing enzalutamide, the patient's platelet count recovered, and he was able to restart the medication without recurrence of thrombocytopenia; however, he later experienced a seizure, suggesting that enzalutamide may also be associated with neurological adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. Murata, M., Takizawa, I., Maruyama, R., et al.[2022]

Enzalutamide (XTANDI) is an FDA-approved treatment for castration-resistant prostate cancer (CRPC) that effectively targets androgen receptor signaling, which is crucial for cancer progression.

In a Phase III clinical trial involving men with CRPC after chemotherapy, enzalutamide was well tolerated and significantly improved overall survival by 4.8 months, as indicated by reduced serum prostate-specific antigen (PSA) levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a novel anti-androgen with prolonged survival rate in CRPC patients. Dhingra, R., Sharma, T., Singh, S., et al.[2021]

In a study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., et al.[2021]

Degarelix is as effective as leuprolide in suppressing testosterone levels in patients with advanced prostate cancer, with faster results and no testosterone surges, based on a 12-month phase III study.

The drug is generally well tolerated, with mild to moderate side effects, making it a viable treatment option for patients needing endocrine therapy for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Degarelix: a review of its use in patients with prostate cancer. Carter, NJ., Keam, SJ.[2021]

References

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

Eyeing Enzalutamide for Hormone-Sensitive Prostate Cancer. [2020]

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

Efficacy of Enzalutamide plus Androgen Deprivation Therapy in Metastatic Hormone-Sensitive Prostate Cancer by Pattern of Metastatic Spread: ARCHES Post Hoc Analyses. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical Outcomes of Enzalutamide in Metastatic Hormone-sensitive Prostate Cancer in Patients Aged [2023]

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

Enzalutamide Bests Older NSAAs in mHSPC. [2021]

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

The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer. [2022]

6. Australia pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. [2022]

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

Enzalutamide: a novel anti-androgen with prolonged survival rate in CRPC patients. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. [2021]

9. Sweden pubmed.ncbi.nlm.nih.gov

Nationwide population-based study on the use of novel antiandrogens in men with prostate cancer in Sweden. [2021]

10. Spain pubmed.ncbi.nlm.nih.gov

Degarelix acetate for the treatment of prostate cancer. [2017]

11. Japan pubmed.ncbi.nlm.nih.gov

Combination of GnRH Antagonist Degarelix and Antiandrogen Is Effective in PSA Reduction and Bone Management in Patients with Prostate Cancer. [2016]

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

Degarelix: a review of its use in patients with prostate cancer. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Degarelix 240/80 mg: a new treatment option for patients with advanced prostate cancer. [2013]