Prostatectomy for Prostate Cancer

Recruiting at 14 trial locations

Overseen By Stephanie Ladd

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

Trial Summary

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.

What data supports the effectiveness of the drug combination of Docetaxel and Androgen Deprivation Therapy for prostate cancer?

Research shows that combining Docetaxel with Androgen Deprivation Therapy (ADT) improves overall survival in men with metastatic prostate cancer, both in hormone-sensitive and castration-resistant stages. This combination has been shown to extend survival and is being evaluated for its potential benefits in high-risk localized prostate cancer as well. ^{1 2 3 4 5}

Is prostatectomy and related treatments generally safe for humans?

Research shows that treatments like docetaxel, used in combination with other therapies for prostate cancer, are generally safe for humans. Studies have found that docetaxel can be safely combined with radiation therapy and hormone therapy, and it is approved by the FDA for use in advanced prostate cancer. ^{2 5 6 7 8}

How is the treatment involving Antiandrogen Therapy, Docetaxel, and Radical Prostatectomy unique for prostate cancer?

This treatment combines hormone therapy (to lower male hormones that fuel cancer growth), docetaxel (a chemotherapy drug that stops cancer cells from dividing), and radical prostatectomy (surgical removal of the prostate), offering a comprehensive approach that targets cancer through multiple mechanisms, which is different from standard treatments that often use these methods separately. ^{6 9 10 11 12}

What is the purpose of this trial?

This randomized phase II trial studies how well surgical removal of the prostate and antiandrogen therapy with or without docetaxel work in treating men with newly diagnosed prostate cancer that has spread to other places in the body. Androgens can cause the growth of prostate cancer cells. Antiandrogen therapy may lessen the amount of androgens made by the body. Drugs used in chemotherapy, such as docetaxel work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Surgery, antiandrogen therapy and docetaxel may work better in treating participants with prostate cancer.

Research Team

Isaac Kim

Principal Investigator

Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Zibotentan for the treatment of castrate-resistant prostate cancer. [2014]

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

Survival Outcomes of Concurrent Treatment with Docetaxel and Androgen Deprivation Therapy in Metastatic Castration-Resistant Prostate Cancer. [2018]

3. United States 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. [2019]

4. United States 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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

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

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

7. England 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. [2019]

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

[Toxicity and efficacy of intermittent docetaxel chemotherapy for hormone refractory prostate cancer]. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Prostate cancer and novel pharmacological treatment options-what's new for 2022? [2023]

10. China pubmed.ncbi.nlm.nih.gov

[Targeted therapies for hormone-refractory prostate cancer]. [2011]

11. Italy pubmed.ncbi.nlm.nih.gov

SEOM clinical guidelines for the treatment of metastatic prostate cancer (2017). [2018]

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

Cabazitaxel for the treatment of prostate cancer. [2014]