Androgen Deprivation + Docetaxel for Prostate Cancer

Overseen By Sara Donadelli

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: TAK-700, Abiraterone

Disqualifiers: Liver metastases, Brain metastases, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 36 months

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a prospective single center phase IIa open label nonrandomized study, which aims to test the hypothesis that the duration of castration sensitive phase of stage IV prostate cancer can be prolonged with adaptive androgen deprivation therapy (ADT) and Docetaxel.

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, you cannot have had certain treatments like TAK-700, abiraterone, apalutamide, or enzalutamide before joining the trial.

What data supports the effectiveness of the drug combination of androgen deprivation and docetaxel for prostate cancer?

Research shows that combining docetaxel with androgen deprivation therapy (ADT) improves survival in patients with advanced prostate cancer, including those with metastatic hormone-sensitive and castration-resistant forms of the disease. ^{1 2 3 4 5}

Is the combination of androgen deprivation and docetaxel safe for prostate cancer treatment?

Docetaxel, also known as Taxotere, has been studied for safety in prostate cancer treatment, often combined with androgen deprivation therapy. While it shows promise in treating prostate cancer, it can cause side effects, especially when combined with other drugs like estramustine, which may increase toxicity (harmful effects). ^{5 6 7 8 9}

How is the drug Docetaxel combined with androgen deprivation therapy unique for prostate cancer treatment?

This treatment is unique because it combines Docetaxel, a chemotherapy drug derived from the European yew tree, with androgen deprivation therapy (ADT) to improve survival in advanced prostate cancer. This combination is particularly effective for patients with high-volume or metastatic hormone-sensitive prostate cancer, offering a novel approach compared to using either treatment alone. ^{1 5 6 9 10}

Research Team

Jingsong Zhang, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

This trial is for men with stage IV prostate cancer that still responds to hormone therapy. Participants should not have had previous chemotherapy for metastatic disease and must be fit enough for Docetaxel treatment. They cannot join if they have allergies that would affect the study or if they've received certain other cancer treatments.

Inclusion Criteria

I haven't had hormone therapy for prostate cancer for more than 4 weeks since it spread.

My prostate cancer was confirmed by a biopsy.

My PSA levels dropped by more than 50% and are now below 4 ng/ml.

Exclusion Criteria

Treatment with any investigational compound within 30 days prior to the first dose of study drugs

I have undergone surgical castration.

I have wounds, ulcers, or bone fractures that are healing slowly.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1-3 visits (in-person)

Treatment

Participants receive adaptive androgen deprivation therapy (ADT) and Docetaxel

36 months

Visits every 4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Docetaxel

Trial Overview The study is testing a combination of hormone-blocking drugs (LHRH analogs and ARSI) with a chemotherapy drug called Docetaxel, aiming to extend the time the cancer remains sensitive to hormone therapy.

Participant Groups

Group I: Adaptive Androgen Deprivation and Docetaxel Treatment Experimental Treatment 3 Interventions

This study will consist of various visits: a screening visit, 1-3 visits during the screening standard of care treatment period and visits every 4 weeks during the adaptive therapy period.

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Findings from Research

In a study involving 376 patients with intermediate- or high-risk prostate cancer, six cycles of adjuvant docetaxel after radical radiotherapy did not improve biochemical disease-free survival compared to surveillance, with similar progression rates in both groups (31% for docetaxel vs. 28% for surveillance).

While 78% of patients completed all six cycles of docetaxel, the treatment was associated with a 16% incidence of febrile neutropenia, but no deaths were directly related to the docetaxel treatment, indicating a safety profile that did not translate into improved outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel Versus Surveillance After Radical Radiotherapy for Intermediate- or High-risk Prostate Cancer-Results from the Prospective, Randomised, Open-label Phase III SPCG-13 Trial. Kellokumpu-Lehtinen, PL., Hjälm-Eriksson, M., Thellenberg-Karlsson, C., et al.[2020]

A systematic review and meta-analysis of 2261 patients showed that adding docetaxel to androgen deprivation therapy significantly improves overall survival, progression-free survival, and failure-free survival in patients with metastatic, hormone-sensitive prostate cancer, with 5-year absolute improvements of around 9-11%.

The benefits of docetaxel are most pronounced in patients with high-volume, clinical T stage 4 disease, while those with low-volume, metachronous disease do not experience meaningful benefits, suggesting that treatment strategies should be tailored based on disease characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which patients with metastatic hormone-sensitive prostate cancer benefit from docetaxel: a systematic review and meta-analysis of individual participant data from randomised trials. Vale, CL., Fisher, DJ., Godolphin, PJ., et al.[2023]

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-based therapy has been shown to provide a survival benefit for men with metastatic prostate cancer, marking a significant advancement beyond palliative care options.

Ongoing trials are exploring various combination therapies with docetaxel, but the best timing for initiating treatment remains unclear due to a lack of prospective clinical trial data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current role of chemotherapy in metastatic hormone-refractory prostate cancer. Petrylak, DP.[2022]

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 153 patients with high-volume metastatic hormone-sensitive prostate cancer, combining docetaxel chemotherapy with androgen-deprivation therapy (ADT) significantly improved progression-free survival (16.9 months vs. 11.2 months for ADT alone) and resulted in a higher PSA response rate (42.9% vs. 13.3% achieving PSA <0.2 ng/ml within 12 months).

While the combination therapy showed promising efficacy, it also led to notable adverse effects, including neutropenia in 61.9% of patients, with 19% experiencing severe cases, indicating that while effective, close monitoring for side effects is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel chemotherapy plus androgen-deprivation therapy in high-volume disease metastatic hormone-sensitive prostate cancer in Chinese patients: an efficacy and safety analysis. Guo, Z., Lu, X., Yang, F., et al.[2022]

In a study of 25 patients with advanced androgen-independent prostate cancer, docetaxel at a higher dose of 100 mg/m showed a 52% overall PSA response rate, with 60% of patients experiencing pain relief.

Despite its efficacy, the treatment had a significant toxicity profile, including severe neutropenia in 76% of patients, indicating that while docetaxel is effective, its use should be cautious and not routine due to the high risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of higher dose docetaxel in androgen-independent prostate cancer. Laber, DA., Glisson, SD., Hargis, JB., et al.[2018]

In a pilot study of 15 patients with hormone-refractory prostate cancer resistant to paclitaxel-based chemotherapy, docetaxel (DTX) showed activity, with 33.3% of patients experiencing a 50% or greater reduction in prostate-specific antigen levels.

Despite its effectiveness, DTX treatment was associated with significant toxicities, including severe anemia in 66.7% of patients, highlighting the need for further research to optimize treatment regimens and manage side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel-based chemotherapy as second-line treatment for paclitaxel-based chemotherapy-resistant hormone-refractory prostate cancer: a pilot study. Urakami, S., Yoshino, T., Kikuno, N., et al.[2018]

Docetaxel shows a 42% response rate in treating androgen-independent prostate cancer based on four Phase II studies, indicating its significant efficacy as a single-agent therapy.

Combining docetaxel with estramustine may enhance response rates but also increases toxicity, and ongoing Phase III studies are expected to clarify the best use of docetaxel in treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (taxotere) in the treatment of prostate cancer. Beer, TM., El-Geneidi, M., Eilers, KM.[2018]

Docetaxel chemotherapy, when combined with androgen deprivation therapy, significantly improves progression-free survival in men with metastatic castrate-sensitive prostate cancer, as shown in pivotal phase III trials (GETUG15, CHAARTED, and STAMPEDE).

CHAARTED and STAMPEDE trials also indicated a clinically meaningful overall survival benefit from docetaxel, making it a valuable treatment option for fit patients starting androgen deprivation therapy for newly diagnosed metastatic prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for metastatic castrate-sensitive prostate cancer. Miller, RE., Sweeney, CJ.[2022]

References

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

Docetaxel Versus Surveillance After Radical Radiotherapy for Intermediate- or High-risk Prostate Cancer-Results from the Prospective, Randomised, Open-label Phase III SPCG-13 Trial. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Which patients with metastatic hormone-sensitive prostate cancer benefit from docetaxel: a systematic review and meta-analysis of individual participant data from randomised trials. [2023]

3. 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]

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

The current role of chemotherapy in metastatic hormone-refractory prostate cancer. [2022]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

Docetaxel chemotherapy plus androgen-deprivation therapy in high-volume disease metastatic hormone-sensitive prostate cancer in Chinese patients: an efficacy and safety analysis. [2022]

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

A phase II study of higher dose docetaxel in androgen-independent prostate cancer. [2018]

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

Docetaxel-based chemotherapy as second-line treatment for paclitaxel-based chemotherapy-resistant hormone-refractory prostate cancer: a pilot study. [2018]

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

Docetaxel (taxotere) in the treatment of prostate cancer. [2018]

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

Chemotherapy for metastatic castrate-sensitive prostate cancer. [2022]