Combination Therapy for Prostate Cancer

Overseen By Jazlyn Heiligh

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must be taking: LHRH analogs

Must not be taking: PD-1 inhibitors

Disqualifiers: Brain metastases, Prostatectomy, Autoimmune disorders, 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 aims to determine if a two-part treatment plan can better assist those with high-risk metastatic prostate cancer. The first part combines hormone therapy, including a Luteinizing Hormone Releasing Hormone and a New Hormonal Agent, with a new drug to reduce cancer activity. The second part adds chemotherapy (Docetaxel) to the regimen. Men with prostate cancer who have certain risk factors—such as a high Gleason score (a measure of cancer aggression), multiple bone metastases (cancer spread to bones), or visible cancer in organs—might be suitable candidates. Participating in this trial could provide a new way to manage their condition. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to explore potentially effective new treatment options.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive medication, you may need to stop it 14 days before starting the study treatment, with some exceptions like certain steroids.

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

Research shows that the treatments in this trial have been tested for safety in humans. Drugs that affect hormone levels, such as LHRH drugs, are often used to treat prostate cancer. They have demonstrated long-term benefits and are usually well-tolerated, though heart-related risks can occur, especially in the first year of treatment.

The new hormone treatments—abiraterone, enzalutamide, and apalutamide—are also well-researched. Studies suggest that enzalutamide, when combined with other treatments, can extend patient survival, though it may carry some heart-related risks. Abiraterone may pose higher heart risks compared to enzalutamide. Apalutamide has proven effective as an initial treatment for prostate cancer.

Docetaxel, a chemotherapy drug used in the trial, is generally effective and tolerable. Some patients may experience side effects such as infections or a low white blood cell count, which can lead to hospitalization. Overall, the treatments have well-documented safety records, though some risks remain. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination therapy for prostate cancer because it offers a two-phase attack strategy that could be more effective than current treatments. The first phase uses a Luteinizing Hormone Releasing Hormone (LHRH) analog with a new hormonal agent to significantly reduce prostate-specific antigen (PSA) levels. If successful, it transitions immediately into a second phase with docetaxel and LHRH analog, adding a layer of targeted chemotherapy. This dual approach may tackle cancer more aggressively and efficiently, especially for patients with persistent cancer markers, who receive additional cycles with docetaxel and the novel immunotherapy agent, tislelizumab. This method could enhance treatment outcomes by combining hormonal, chemotherapeutic, and immunotherapy strategies, potentially leading to better long-term control of the disease.

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

Research has shown that certain treatments can greatly benefit prostate cancer patients. In this trial, participants will undergo a "first strike" treatment using Luteinizing Hormone Releasing Hormone (LHRH) analogs combined with a new hormonal agent, which can lower prostate-specific antigen (PSA) levels and improve symptoms in about 90% of patients. Long-term use of LHRH agonists has been linked to better survival rates. The "second strike" involves the chemotherapy drug docetaxel, which can significantly reduce the risk of dying from prostate cancer and help patients live longer. This combined treatment approach aims to enhance the effectiveness of each method, especially for those with high-risk metastatic prostate cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Jingsong Zhang, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for men with high-risk, stage IV prostate cancer who haven't had extensive prior treatments. They should be relatively healthy (ECOG 0-1), have not used certain hormone therapies recently, and must agree to use contraception. Men with uncontrolled heart issues, recent investigational drugs, brain metastases, or autoimmune diseases are excluded.

Inclusion Criteria

My prostate cancer diagnosis was confirmed through a biopsy.

I am fully active or can carry out light work.

My prostate cancer is high risk with a Gleason score of 8+, 3+ bone metastases, or visceral metastasis.

Exclusion Criteria

I have a history of lung conditions like interstitial lung disease or pulmonary fibrosis.

History of severe hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins

I have had surgery to remove my prostate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

First Strike

Participants receive combined therapy with LHRH analog and one of the new hormonal agents for 12-18 weeks

12-18 weeks

Second Strike

Participants receive 4 cycles of docetaxel and LHRH analog, with potential consolidation therapy based on biopsy results

12-18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including PSA and radiographic progression assessments

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Luteinizing Hormone Releasing Hormone
• New Hormonal Agent

Trial Overview The study tests if starting treatment with hormonal therapy (LHRH analog plus a new agent like abiraterone) followed by chemotherapy (docetaxel) improves outcomes in advanced prostate cancer. Participants will first receive the hormonal therapy then move on to chemohormonal therapy.

How Is the Trial Designed?

Group I: First Strike then Second Strike Experimental Treatment 4 Interventions

The first part of the study treatment or "first strike" involves 12-18 weeks of combined therapy with LHRH analog and one of the new hormonal agents (NHAs). Participants will complete the "first strike" at week 13 if their PSA has reduced \>90%; otherwise they will complete a total of 18 weeks of therapy. The second part of the treatment or "second strike" involves 4 cycles docetaxel and LHRH analog. The "second strike" will start immediately after the "first strike". MRI guided prostate biopsy will be performed after "second strike". For patients with positive prostate biopsy or detectable PSA, the "second strike" will be consolidated with 4-6 additional cycles of docetaxel plus 6 doses of tislelizumab at 200 mg, given IV once every 3 weeks. For patients with undetectable PSA at year 3 from study enrollment, LHRH analog can be discontinued.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

BeiGene

Industry Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

In a randomized trial involving 813 patients with Stage D2 prostate carcinoma, bicalutamide combined with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy showed equivalent efficacy to flutamide combined with LHRH-A, with similar time to disease progression over a median follow-up of 95 weeks.

The analysis indicated that both treatment regimens had comparable outcomes, with a hazard ratio of 0.9, suggesting that bicalutamide is as effective as flutamide in delaying disease progression in prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate carcinoma. Analysis of time to progression. CASODEX Combination Study Group. Schellhammer, PF., Sharifi, R., Block, NL., et al.[2019]

In a phase II study involving 62 advanced prostate cancer patients, high-dose estetrol (HDE4) combined with androgen deprivation therapy (ADT) significantly reduced the frequency and severity of hot flushes, with only 13.5% of patients experiencing weekly hot flushes compared to 60% in the placebo group.

HDE4 treatment also led to a more rapid and profound suppression of total and free testosterone, prostate-specific antigen (PSA), and follicle-stimulating hormone (FSH), while showing no serious cardiovascular adverse events, indicating its potential for enhanced disease control and safety in ADT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estetrol Cotreatment of Androgen Deprivation Therapy in Infiltrating or Metastatic, Castration-sensitive Prostate Cancer: A Randomized, Double-blind, Phase II Trial (PCombi). Coelingh Bennink, HJT., van Moorselaar, JA., Crawford, ED., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40276087/

Real‑world data on the outcomes of upfront docetaxel in ... The present study demonstrated that upfront docetaxel chemotherapy may be an effective and tolerable treatment for hormone-sensitive metastatic ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2589004225005103

Article Real-world effectiveness of novel hormonal agents ... Our results indicate that patients treated with NHAs experience comparable OS and PSA-PFS to those treated with docetaxel, yet they require less ...

3. brighamhealthonamission.org brighamhealthonamission.org/2023/11/06/docetaxel-found-to-be-significantly-associated-with-reduced-prostate-cancer-mortality-in-patients-with-otherwise-poor-prognosis/

Docetaxel Found to Be Significantly Associated With ... SOC plus docetaxel was associated with a significant 70% reduction in prostate cancer-specific mortality (PCSM) and a nearly halved all-cause mortality.

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2811171

Mortality Risk for Docetaxel-Treated, High-Grade Prostate ... Docetaxel has been shown to prolong overall survival (OS) in men with castrate-resistant and castrate-sensitive metastatic prostate cancer.

5. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14575-1

Assessing the clinical outcomes of immunotherapy and ... Assessing the clinical outcomes of immunotherapy and docetaxel combinations in metastatic castration-resistant prostate cancer: a meta-analysis.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28940952/

Real-world uptake, safety profile and outcomes of ... Results: Of the 270 eligible patients, 103 received docetaxel (38.1%). 35 patients (34%) were hospitalised and there were 17 episodes of febrile neutropenia ( ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12018791/

Real‑world data on the outcomes of upfront docetaxel ... The present study demonstrated that upfront docetaxel chemotherapy may be an effective and tolerable treatment for hormone-sensitive metastatic prostate cancer.

8. ascopubs.org ascopubs.org/doi/10.1200/JGO.2016.007807

Efficacy and Safety of Docetaxel in Elderly Patients With ... Administration of docetaxel in elderly patients who had good performance status was well tolerated. Rates of PSA decline and TTP were similar to those of ...