Prostatectomy for Prostate Cancer

Recruiting at 16 trial locations

Overseen By Laura Kane

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Rutgers, The State University of New Jersey

Must be taking: Antiandrogen therapy

Disqualifiers: Unresectable disease, Life expectancy, DVT/PE, 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: At least 1 month

190 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining prostate removal surgery with antiandrogen therapy, with or without the chemotherapy drug docetaxel, for treating prostate cancer that has spread. Antiandrogen therapy reduces hormones that fuel cancer growth, while docetaxel stops cancer cells from growing. Men diagnosed with prostate cancer that has spread and have not yet received local treatments like radiation may be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chemotherapy or radiotherapy for non-prostate cancer treatment, you must not have received it within 3 weeks before joining the trial.

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

Research has shown that antiandrogen therapy is usually well-tolerated, though some patients might experience side effects such as diarrhea, hot flashes, or decreased sexual desire. Many patients experience a reduction in prostate-specific antigen (PSA) levels, indicating the treatment's effectiveness.

Studies have found that docetaxel, a chemotherapy drug, can cause side effects like fever with low white blood cell counts, potentially leading to hospital stays. Despite this, it is considered effective for treating prostate cancer, and many patients tolerate it well.

Research on radical prostatectomy, the surgical removal of the prostate, suggests it is safe and practical, with few complications. This surgery is often recommended for prostate cancer and can reduce deaths specifically related to the cancer.

In summary, while each treatment can have side effects, they are generally manageable, and the treatments are effective against prostate cancer. Patients should always discuss any concerns or questions with a doctor. ^{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 combine antiandrogen therapy, docetaxel, and radical prostatectomy in a novel way. Most standard treatments for prostate cancer focus on either hormone therapy or surgery alone. However, this approach integrates hormone therapy with surgery and chemotherapy, potentially enhancing the effectiveness against the cancer. The use of docetaxel, a chemotherapy drug, before surgery is particularly intriguing, as it may shrink tumors and improve surgical outcomes. This comprehensive strategy could offer better control of the disease and improve overall survival rates for patients.

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

Research has shown that combining antiandrogen therapy with the drug docetaxel can improve outcomes for men with prostate cancer that has spread and still responds to hormones. In this trial, participants in Arm I will receive antiandrogen therapy with or without docetaxel, while those in Arm II will receive antiandrogen therapy, radical prostatectomy, and may receive docetaxel. Studies indicate that adding docetaxel to antiandrogen therapy significantly increases overall survival compared to using antiandrogen therapy alone, providing a 9% absolute benefit in remaining cancer-free for five years. Surgery to remove the prostate, known as radical prostatectomy, can also help reduce death rates from prostate cancer. The Scandinavian Prostate Cancer Study found an 11.7% decrease in deaths from prostate cancer with this surgery. Together, these treatments aim to control cancer growth and improve survival. ^{4 6 7 8 9}

Who Is on the Research Team?

Isaac Kim, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

Men with newly diagnosed metastatic prostate cancer who have started or plan to start antiandrogen therapy within the last 6 months. They must not have had previous local treatments for prostate cancer, should be able to undergo surgery, and have a life expectancy of more than 6 months. Their blood counts and liver enzymes need to be at certain levels, and they must be physically well enough (ECOG status of 0 or 1).

Inclusion Criteria

My single cancer spread was confirmed by biopsy or two different scans.

My surgeon has determined my prostate can be surgically removed.

I started hormone therapy for cancer less than 6 months ago.

Exclusion Criteria

Your doctor believes that you have less than 6 months to live.

My surgeon says my cancer cannot be removed by surgery.

I have had a blood clot in my leg or lung in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive antiandrogen therapy with or without docetaxel, and may undergo cytoreductive radical prostatectomy

At least 1 month

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 6 months from time of progression

What Are the Treatments Tested in This Trial?

Interventions

• Antiandrogen Therapy
• Docetaxel
• Radical Prostatectomy

Trial Overview The trial is testing if removing the prostate gland surgically combined with hormone-blocking therapy works better with or without docetaxel chemotherapy in men whose prostate cancer has spread. The study will compare how these different treatments affect tumor growth by killing cells, stopping cell division, or preventing spread.

How Is the Trial Designed?

Group I: Arm II (ADT, radical prostatectomy, docetaxel) Experimental Treatment 6 Interventions

Participants receive antiandrogen therapy for at least 1 month, then undergo cytoreductive radical prostatectomy. Participants continue antiandrogen therapy and may receive docetaxel prior to surgery at the discretion of the treating physician.

Group II: Arm I (ADT, docetaxel) Experimental Treatment 5 Interventions

Participants receive antiandrogen therapy with or without docetaxel at the discretion of the treating physician.

Antiandrogen Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Antiandrogen Therapy for:

• Prostate cancer

Approved in European Union as Antiandrogen Therapy for:

• Prostate cancer

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 46 patients with hormone refractory prostate cancer (HRPC) who had previously responded to docetaxel, 56% achieved a significant PSA response of over 50% after receiving intermittent docetaxel chemotherapy, indicating its efficacy in this patient group.

The median overall survival for patients receiving at least two cycles of docetaxel was 35 months, and the treatment was well tolerated, with no significant increase in toxicity, suggesting that intermittent docetaxel can be a viable option for managing HRPC after initial treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Toxicity and efficacy of intermittent docetaxel chemotherapy for hormone refractory prostate cancer]. Olbert, PJ., Weil, C., Hegele, A., et al.[2018]

In a study of 47 men with metastatic castration-resistant prostate cancer (mCRPC), combining androgen deprivation therapy (ADT) with docetaxel chemotherapy (DTX) significantly improved radiographic progression-free survival (rPFS) compared to DTX alone, with median rPFS of 9.0 months versus 6.0 months.

While overall survival (OS) was similar between the two groups (42.0 months for DTX+ADT and 38.0 months for DTX), the study indicates that concurrent ADT with DTX is a beneficial strategy for improving disease control in mCRPC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Outcomes of Concurrent Treatment with Docetaxel and Androgen Deprivation Therapy in Metastatic Castration-Resistant Prostate Cancer. Jang, HS., Koo, KC., Cho, KS., et al.[2018]

Androgen deprivation treatment was the only option for metastatic prostate cancer until recently, but now multiple drugs, including docetaxel, sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, and radium-223, have been approved for castration-resistant prostate cancer (CRPC).

Docetaxel and abiraterone have been successfully introduced in the treatment of hormone-sensitive prostate cancer, leading to improved survival rates for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SEOM clinical guidelines for the treatment of metastatic prostate cancer (2017). Cassinello, J., Arranz, JÁ., Piulats, JM., et al.[2018]

Endothelin-1 (ET-1) is a crucial factor in the growth and metastasis of prostate cancer, making it a promising target for new treatments, especially in patients with castration-resistant prostate cancer.

Zibotentan, a selective inhibitor of the ET(A) receptor, has shown promising results in Phase II trials and is currently being evaluated in three ongoing Phase III trials to assess its impact on overall survival in patients with metastatic prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zibotentan for the treatment of castrate-resistant prostate cancer. Shepard, DR., Dreicer, R.[2014]

Docetaxel is the first treatment to significantly improve survival rates in patients with hormone-refractory prostate cancer, and it is now being tested in earlier stages of the disease to prevent recurrence in high-risk patients.

Pilot studies indicate that using docetaxel as a neo-adjuvant treatment can be done safely without increasing surgical risks, and ongoing randomized trials will further assess its effectiveness when combined with hormonal therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-risk localized prostate cancer: integrating chemotherapy. Oh, WK.[2018]

In a Phase I study involving 18 patients with high-risk prostate cancer, the addition of weekly docetaxel chemotherapy at a safe dose of 20 mg/m² to high-dose intensity-modulated radiation therapy (IMRT) and androgen-deprivation therapy (ADT) was found to be safe, with no severe toxicities reported.

At a median follow-up of 2.2 years, the treatment resulted in a high biochemical progression-free survival rate of 94%, indicating promising efficacy for this triple-therapy regimen in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of concurrent weekly docetaxel, high-dose intensity-modulated radiation therapy (IMRT) and androgen-deprivation therapy (ADT) for high-risk prostate cancer. Chen, RC., Rosenman, JG., Hoffman, LG., et al.[2019]

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]

In a study of 773 men with metastatic hormone-sensitive prostate cancer, the combination of docetaxel and androgen deprivation therapy (ADT) showed similar progression-free survival (PFS) and overall survival (OS) benefits across different age groups, indicating its efficacy regardless of age.

Older men (over 70 years) experienced a modest increase in the number of adverse events compared to younger men, suggesting that while the treatment is effective, careful consideration of potential side effects is crucial for older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Adverse Events of Docetaxel for Metastatic, Hormone-sensitive Prostate Cancer Among Elderly Men: A Post Hoc Analysis of the CHAARTED Trial. Li, EV., Siddiqui, MR., Weiner, AB., et al.[2022]

Cabazitaxel is emerging as a promising second-line chemotherapy option for patients with castration-resistant prostate cancer (CRPC), following the first-line treatment with docetaxel.

The review highlights the importance of focusing on quality of life in treatment strategies for CRPC, suggesting that while cabazitaxel shows potential, further research is needed to fully establish its efficacy and safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel for the treatment of prostate cancer. Michielsen, DP., Braeckman, JG., Denis, L.[2014]

In a study of 132 patients with high-risk localized prostate cancer, adding weekly docetaxel to radiation therapy and androgen deprivation did not significantly improve biochemical recurrence-free survival compared to standard treatment alone.

The combination treatment was found to be safe, with no significant increase in toxicity, and both treatment arms showed similar long-term survival rates, indicating that while docetaxel can be safely administered, it may not provide additional benefits in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 Randomized Study of Radiation Therapy and 3-Year Androgen Deprivation With or Without Concurrent Weekly Docetaxel in High-Risk Localized Prostate Cancer Patients. Carles, J., Gallardo, E., Doménech, M., et al.[2019]

Recent trials suggest that combining androgen deprivation therapy (ADT) with chemotherapy and androgen receptor-targeted agents (ARTAs) may be particularly effective for treating metastatic hormone-sensitive prostate cancer, indicating a promising direction for future therapies.

The radionuclide 177Lu-PSMA-617 has shown successful outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC), highlighting its potential as a valuable treatment option in advanced disease settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate cancer and novel pharmacological treatment options-what's new for 2022? Marchetti, A., Tassinari, E., Rosellini, M., et al.[2023]

Prostate cancer often becomes resistant to androgen withdrawal therapy, making it crucial to explore new treatment options for hormone-refractory prostate cancer (HRPC).

Current standard treatment for HRPC involves a combination of docetaxel and prednisone, but there is no established second-line therapy; the article reviews promising new drugs targeting various pathways to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Targeted therapies for hormone-refractory prostate cancer]. Song, HZ., Chen, LB.[2011]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7076308/

Efficacy of Androgen Deprivation Therapy in Patients with ... The purpose of this study was to determine the comparative effectiveness of androgen deprivation therapy (ADT) combined with docetaxel (DTX)-based chemotherapy

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9892544/

Effectiveness of Adding Docetaxel to Androgen Deprivation ... Evidence in favor of adding docetaxel in treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has led to docetaxel in conjunction with androgen ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1503747

Chemohormonal Therapy in Metastatic Hormone-Sensitive ... Six cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2588931124000282

A 3-year Interim Analysis of the Observational J-ROCK Study In this study, we compared clinical and safety outcomes with different treatment regimens, using a large series of patients with high-risk metastatic hormone- ...

5. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00230-9/fulltext

Which patients with metastatic hormone-sensitive prostate ... Absolute benefit of docetaxel was 9% (95% CI 6–12) on 5-year failure-free survival, increasing it from 14% (13–16) with ADT alone to 23% (21–26) with ADT plus ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11479264/

a systematic review and network meta-analysis - PMC This systematic review and network meta-analysis aimed to assess the comparative effectiveness and safety profiles of current combination ...

7. ascopubs.org ascopubs.org/doi/10.1200/EDBK_433126

Balancing Hormone Therapy: Mitigating Adverse Effects of ... Treatment advances including ADT have led to improvements in PCa management and survival, with trials reporting median survival of over 6 years ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4094624/

Androgen deprivation therapy for prostate cancer: long-term ... ADT can normalize serum prostate specific antigen in over 90% of patients and results in sizable tumor response in 80% to 90%. This treatment can be done either ...

9. cancer.gov cancer.gov/types/prostate/prostate-hormone-therapy-fact-sheet

Hormone Therapy for Prostate Cancer Fact Sheet - NCI Antiandrogens can cause diarrhea, breast tenderness, nausea, hot flashes, loss of libido, and erectile dysfunction. The antiandrogen flutamide ...