Chemoimmunotherapy + Hormone Therapy for Prostate Cancer

Overseen By Research Nurse Navigator

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Mark Stein

Must be taking: 5-alpha reductase inhibitors

Must not be taking: Immunotherapy, Chemotherapy

Disqualifiers: Autoimmune disease, HIV, Hepatitis, 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

26 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective is to determine the safety and activity of combined hormonal chemoimmunotherapy in a single-arm phase II trial of REGN2810, androgen deprivation therapy (ADT), and docetaxel in patients with newly metastatic, hormone-sensitive prostate cancer (mHSPC), using a primary endpoint of undetectable prostate-specific antigen (PSA) at 6 months, defined from start of combination therapy (week 10) until 6 months (week 37).

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on androgen receptor inhibitors, you will need to stop them for the duration of the study. If you are taking 5-alpha reductase inhibitors, you should continue them during the study.

What data supports the effectiveness of the drug leuprolide acetate in treating prostate cancer?

Research shows that leuprolide acetate, a drug used in hormone therapy, effectively lowers testosterone levels in patients with prostate cancer, which helps control the disease. It is as effective as surgical castration in reducing testosterone and has been used successfully for over 20 years. ^{1 2 3 4 5}

Is the combination of chemoimmunotherapy and hormone therapy for prostate cancer safe?

Docetaxel, a key drug in this treatment, is generally safe but can cause side effects like low white blood cell counts, hair loss, mouth sores, diarrhea, and nerve damage. Using a growth factor can help reduce the risk of serious infections in older patients. ^{6 7 8 9 10}

What makes the Chemoimmunotherapy + Hormone Therapy for Prostate Cancer unique?

This treatment combines chemotherapy, immunotherapy, and hormone therapy, which is unique because it targets prostate cancer from multiple angles, potentially improving outcomes compared to using just one type of therapy. It includes drugs like Degarelix and Docetaxel, which are standard in prostate cancer treatment, but adds REGN2810, an immunotherapy, to enhance the body's immune response against cancer cells. ^{7 11 12 13 14}

Research Team

Mark N. Stein

Principal Investigator

Columbia University

Eligibility Criteria

Men over 18 with newly metastatic, hormone-sensitive prostate cancer who haven't had certain treatments like androgen deprivation therapy or chemotherapy for prostate cancer in the last 6 months. They should have a life expectancy over a year, good organ function, no severe allergies to trial drugs, and agree to use contraception.

Inclusion Criteria

- Platelets ≥100,000

- Leukocytes ≥3,000/microliters (mcL)

I agree to use contraception during and 4 months after the study due to unknown effects on fetuses.

Exclusion Criteria

I have Hepatitis B under control with a viral load under 100 IU/mL.

I have had an organ or bone marrow transplant.

My nerve damage symptoms are mild or not present.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Androgen Deprivation Therapy (ADT)

Initiate degarelix 240mg SC once, followed by leuprolide acetate 22.5mg SC every 3 months

10 weeks

Chemoimmunotherapy

Start cemiplimab (REGN 2810) 350mg IV every 3 weeks for up to 55 weeks or until intolerable side effects or disease progression. Start docetaxel 75 mg/m2 every 21 days for up to 6 cycles

55 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Degarelix
• Docetaxel
• Leuprolide Acetate
• REGN2810

Trial Overview The trial is testing REGN2810 combined with hormonal therapy (Degarelix or Leuprolide Acetate) and Docetaxel chemotherapy. The goal is to see if this mix can make prostate-specific antigen levels undetectable after six months of treatment.

Participant Groups

Group I: ADT Followed by Chemoimmunotherapy Experimental Treatment 4 Interventions

REGN2810 followed by chemoimmunotherapy: Initiate degarelix 240mg SC once, followed by leuprolide acetate 22.5mg SC every 3 months. Week 4 start cemiplimab (REGN 2810) 350mg IV every 3 weeks (flat dose) for up to 55 weeks or intolerable side effect or progression of disease. Week 10 start docetaxel 75 mg/m2 every 21 days for up to 6 cycles.

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?

Mark Stein

Lead Sponsor

Trials

4

Recruited

150+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

In a study involving 1,906 patients with advanced prostate cancer, both 3-month and 6-month leuprorelin acetate depot formulations significantly reduced prostate-specific antigen (PSA) levels from an average of 12.0 ng/mL to 0.5 ng/mL after 12 months, indicating effective treatment.

The treatment was well-tolerated, with only 8.8% of patients experiencing adverse events, suggesting that leuprorelin acetate is a safe option for managing advanced prostate cancer in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Leuprorelin Acetate (Eligard®) in Daily Practice in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or 6-Month Depot Formulations in Patients with Advanced Prostate Cancer. Ohlmann, CH., Gross-Langenhoff, M.[2018]

In a 6-month study involving 117 patients with prostate cancer, the 3-month subcutaneous depot of leuprolide acetate (LA-2550) effectively suppressed serum testosterone levels to below 50 ng/dl in 98% of patients by day 28, and all patients achieved this level by day 35.

The treatment was well-tolerated, with no flare reactions and minimal adverse effects, primarily mild to moderate hot flashes, indicating a favorable safety profile while achieving significant reductions in testosterone and prostate-specific antigen levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical study of 22.5 mg. La-2550: A new subcutaneous depot delivery system for leuprolide acetate for the treatment of prostate cancer. Chu, FM., Jayson, M., Dineen, MK., et al.[2023]

Docetaxel is an effective treatment for hormone-refractory prostate cancer (HRPC), showing significant anti-tumor effects as a single agent and even more when combined with other drugs like estramustine.

The FDA approved docetaxel in combination with prednisone in 2004 for advanced metastatic prostate cancer, highlighting its established role in treatment despite the challenge of hormone resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of androgen-independent hormone refractory prostate cancer using docetaxel]. Miyoshi, Y., Uemura, H., Kubota, Y.[2018]

Recent trials have shown that combining enzalutamide or apalutamide with androgen deprivation therapy (ADT) significantly improves survival in patients with metastatic castration-sensitive prostate cancer, expanding treatment options beyond docetaxel and abiraterone acetate.

Emerging evidence also supports the use of radiotherapy for the primary tumor in metastatic prostate cancer, suggesting a more personalized approach to treatment based on individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving options in metastatic castration-sensitive prostate cancer. Hamilou, Z.[2021]

Cabazitaxel is an effective second-line chemotherapy for metastatic castration-resistant prostate cancer, but it carries a risk of neutropenic complications, especially in frail elderly patients.

Using prophylactic granulocyte colony-stimulating factor from the first treatment cycle can help improve the safety and efficacy of cabazitaxel, and alternative dosing schedules are being explored to benefit frail patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel schedules in metastatic castration-resistant prostate cancer: a review. Pobel, C., Auclin, E., Procureur, A., et al.[2021]

Sipuleucel-T has shown to improve overall survival by 4 months in patients with castration-resistant prostate cancer, particularly benefiting those with favorable prognostic factors like minimal tumor burden and a Gleason score of ≤7.

New immunomodulatory treatments like ipilimumab and tasquinimod, along with antihormonal drugs such as abiraterone acetate, are emerging as promising options for managing castration-resistant prostate cancer, indicating a shift towards more effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for metastatic prostate cancer: do we really need this?]. Heidenreich, A.[2021]

Docetaxel chemotherapy is a standard first-line treatment for castration-resistant prostate cancer, providing a modest overall survival benefit of 2 months, but patients typically progress to a docetaxel-insensitive phase within 6-9 months.

Emerging therapies like cabazitaxel, sipuleucel-T, and abiraterone show promise for secondary treatment options, highlighting the need for more clinical data to explore various combinations and sequences of therapies for better outcomes in specific patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Second line therapy for castration-resistant prostate cancer (CRPC)]. Molitor, B., Börgermann, C.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Leuprorelin Acetate (Eligard®) in Daily Practice in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or 6-Month Depot Formulations in Patients with Advanced Prostate Cancer. [2018]

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

A clinical study of 22.5 mg. La-2550: A new subcutaneous depot delivery system for leuprolide acetate for the treatment of prostate cancer. [2023]

3. India pubmed.ncbi.nlm.nih.gov

Leuprorelin acetate in prostate cancer: a European update. [2022]

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

Eligard: leuprolide acetate in a novel sustained-release delivery system. [2019]

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

A six-month, open-label study assessing a new formulation of leuprolide 7.5 mg for suppression of testosterone in patients with prostate cancer. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

[Treatment of androgen-independent hormone refractory prostate cancer using docetaxel]. [2018]

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

New treatments for metastic prostate cancer. [2016]

8. France pubmed.ncbi.nlm.nih.gov

[Chemotherapy in castrate-resistant metastatic prostate cancer]. [2013]

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

The evolving options in metastatic castration-sensitive prostate cancer. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Cabazitaxel schedules in metastatic castration-resistant prostate cancer: a review. [2021]

11. Germany pubmed.ncbi.nlm.nih.gov

[Immunotherapy for metastatic prostate cancer: do we really need this?]. [2021]

12. Germany pubmed.ncbi.nlm.nih.gov

[Second line therapy for castration-resistant prostate cancer (CRPC)]. [2021]

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

Intermittent Chemotherapy as a Platform for Testing Novel Agents in Patients With Metastatic Castration-Resistant Prostate Cancer: A Department of Defense Prostate Cancer Clinical Trials Consortium Randomized Phase II Trial of Intermittent Docetaxel With Prednisone With or Without Maintenance GM-CSF. [2020]

14. France pubmed.ncbi.nlm.nih.gov

[Strategy in advanced castration-resistant prostate cancer]. [2018]