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

32 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical research is to find if sequential therapy with combined androgen deprivation or hormonal therapy with luteinizing hormone release hormone (LHRH) analog plus a new hormonal agent (abiraterone, enzalutamide, or apalutamide) followed by chemohormonal therapy with docetaxel and LHRH analog would improve the outcome of high risk metastatic/stage IV prostate cancer.

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.

What data supports the effectiveness of the combination therapy for prostate cancer involving Docetaxel, Taxotere, Docefrez, Docivyx, DTX, DXL, Luteinizing Hormone Releasing Hormone, and New Hormonal Agent?

Research shows that combining a luteinizing hormone-releasing hormone (LHRH) agonist with other treatments, like antiandrogens, can significantly extend survival and delay disease progression in prostate cancer patients compared to using LHRH agonists alone. ^{1 2 3 4 5}

What safety data exists for combination therapy using LHRH agonists in prostate cancer treatment?

Luteinizing hormone-releasing hormone (LHRH) agonists, used in prostate cancer treatment, can decrease bone mineral density, increasing the risk of bone fractures. Some patients may experience side effects like hot flashes, loss of libido, and impotence. Overall, these treatments are generally well tolerated, with low incidence of severe side effects. ^{6 7 8 9 10}

How is the combination therapy for prostate cancer different from other treatments?

This combination therapy for prostate cancer is unique because it combines a luteinizing hormone-releasing hormone (LHRH) agonist with a new hormonal agent, potentially improving the effectiveness of androgen deprivation therapy (ADT) by targeting hormone pathways more comprehensively. This approach may offer better control of prostate cancer progression compared to using LHRH agonists alone. ^{1 6 11 12 13}

Research Team

Jingsong Zhang, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. Netherlands 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). [2022]

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

Early development of castrate resistance varies with different dosing regimens of luteinizing hormone releasing hormone agonist in primary hormonal therapy for prostate cancer. [2013]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Combination studies with leuprolide. [2019]

4. Japan pubmed.ncbi.nlm.nih.gov

[The effects of LH-RH agonist alone or with flutamide in the treatment of stage D2 prostate cancer]. [2013]

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

Combination therapy for prostate cancer. Endocrine and biologic basis of its choice as new standard first-line therapy. [2019]

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

Bone fractures associated with luteinizing hormone-releasing hormone agonists used in the treatment of prostate carcinoma. [2019]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Is high-dose leuprorelin acetate effective and safe in asian men with prostate cancer? An open-label, non-comparative, multi-center clinical trial. [2022]

8. Italy pubmed.ncbi.nlm.nih.gov

[Neoadjuvant combined hormonal therapy and radiotherapy with external beam irradiation in prostatic carcinoma]. [2013]

9. Japan pubmed.ncbi.nlm.nih.gov

Inhibition of PSA flare in prostate cancer patients by administration of flutamide for 2 weeks before initiation of treatment with slow-releasing LH-RH agonist. [2022]

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

Buserelin treatment of advanced prostatic carcinoma. Long-term follow-up of antitumor responses and improved quality of life. [2019]

11. United States 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. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Bicalutamide 80 mg combined with a luteinizing hormone-releasing hormone agonist (LHRH-A) versus LHRH-A monotherapy in advanced prostate cancer: findings from a phase III randomized, double-blind, multicenter trial in Japanese patients. [2022]

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

Combined androgen blockade with bicalutamide for advanced prostate cancer: long-term follow-up of a phase 3, double-blind, randomized study for survival. [2022]