ADT + Docetaxel + Enzalutamide for Prostate Cancer

Overseen By Sandra Samu-Arce, RN

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Earle Burgess, MD

Must be taking: Androgen deprivation therapy

Must not be taking: Ketoconazole, Abiraterone, Enzalutamide, others

Disqualifiers: Seizure history, CNS 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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a study with the combination of androgen deprivation therapy (ADT) and docetaxel with the addition of enzalutamide in the treatment of subjects with metastatic prostate cancer. The purpose of this study is to assess if ADT + docetaxel + enzalutamide is well tolerated and demonstrates improved efficacy compared to ADT + docetaxel.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot participate if you are using certain medications like ketoconazole, abiraterone, or strong CYP2C8 inhibitors. It's best to discuss your current medications with the trial team to see if they are allowed.

What data supports the effectiveness of the drug combination ADT, Docetaxel, and Enzalutamide for prostate cancer?

Research shows that combining docetaxel with androgen deprivation therapy (ADT) improves survival in men with metastatic, hormone-sensitive prostate cancer. Additionally, enzalutamide has been linked to better survival in men with castration-resistant prostate cancer, suggesting potential benefits when added to ADT and docetaxel. ^{1 2 3 4 5}

Is the combination of ADT, Docetaxel, and Enzalutamide safe for treating prostate cancer?

Research shows that docetaxel is safe when used with radiation therapy and ADT for prostate cancer, and enzalutamide is approved for use in certain prostate cancer cases, indicating these treatments are generally safe in humans. ^{1 6 7 8 9}

How is the ADT + Docetaxel + Enzalutamide treatment for prostate cancer different from other treatments?

This treatment combines hormone therapy (ADT), chemotherapy (Docetaxel), and a drug that blocks male hormones (Enzalutamide) to improve survival in men with advanced prostate cancer. The combination targets cancer cells more effectively by attacking them in multiple ways, which is different from using hormone therapy alone. ^{2 3 10 11 12}

Research Team

Earle Burgess, MD

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

Men aged 18+ with metastatic prostate cancer, a PSA level of ≥5 ng/ml, and good performance status (ECOG 0-2) can join. They should have started hormone therapy recently or had it before for non-metastatic disease. Participants need proper liver, kidney, and bone marrow function and must be able to take oral meds. Those with severe neuropathy, active infections like HIV or hepatitis B/C, recent heart issues, another active cancer within the last year, conditions that could cause seizures or affect drug absorption are excluded.

Inclusion Criteria

My liver tests are within normal limits.

My prostate cancer has spread and is not mainly neuroendocrine or small cell type.

I started hormone therapy for cancer less than 112 days ago.

Exclusion Criteria

I do not have HIV or active hepatitis B or C.

I haven't had a heart attack, severe chest pain, heart surgery, heart failure, or stroke in the last 3 months.

I have not had any other cancer besides this one in the last year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive androgen deprivation therapy, docetaxel, and enzalutamide

52 weeks

Regular visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ADT
• Docetaxel
• Enzalutamide

Trial Overview The trial is testing if combining hormone therapy (ADT), chemotherapy (docetaxel), and a targeted drug (enzalutamide) works better for advanced prostate cancer than just ADT with chemo. It's checking how well patients tolerate this mix and if it improves their condition.

Participant Groups

Group I: Single Arm Experimental Treatment 1 Intervention

Docetaxel + Enzalutamide + Androgen Deprivation Therapy

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

Approved in European Union as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in United States as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in Canada as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in Japan as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in China as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in Switzerland as Androgen Deprivation Therapy for:

• Prostate Cancer

Who Is Running the Clinical Trial?

Earle Burgess, MD

Lead Sponsor

Trials

2

Recruited

50+

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Astellas Pharma Inc

Industry Sponsor

Trials

700

Recruited

236,000+

Headquarters

Tokyo, Japan

Top Products

- Xtandi (enzalutamide) for prostate cancer, - Xospata (gilteritinib) for AML, - Padcev (enfortumab vedotin) for bladder cancer, - Prograf (tacrolimus) for organ rejection prevention

Tadaaki Taniguchi

Astellas Pharma Inc

Chief Medical Officer since 2023

MD, PhD

Naoki Okamura

Astellas Pharma Inc

Chief Executive Officer since 2023

University of Tokyo, Faculty of Pharmacy

Medivation, Inc.

Industry Sponsor

Trials

76

Recruited

11,200+

Dr. David Hung

Medivation, Inc.

Chief Executive Officer since 2003

MD from University of California, San Francisco; AB in Biology from Harvard College

Dr. Stephen M. Kelsey

Medivation, Inc.

Chief Medical Officer since 2013

MD from University of Birmingham

Findings from Research

The FDA has approved the combination of mitoxantrone and prednisone for hormone-refractory prostate cancer due to its superior palliative effects compared to steroids alone, based on two randomized trials.

A new phase III trial by the Southwest Oncology Group will compare the effectiveness of estramustine plus docetaxel against the standard treatment of mitoxantrone and prednisone, focusing on time to progression and survival, while also evaluating side effects and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) and estramustine versus mitoxantrone and prednisone for hormone-refractory prostate cancer: scientific basis and design of Southwest Oncology Group Study 9916. Hussain, M., Petrylak, D., Fisher, E., et al.[2018]

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]

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]

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 phase 3 trial involving 1125 men with metastatic, hormone-sensitive prostate cancer, adding enzalutamide to testosterone suppression significantly improved overall survival, with a 3-year survival rate of 80% compared to 72% in the standard-care group.

While enzalutamide showed better progression-free survival and overall survival, it was associated with a higher incidence of adverse effects, including fatigue and seizures, particularly in patients also receiving early docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. Davis, ID., Martin, AJ., Stockler, MR., et al.[2021]

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 phase 2 study involving 67 men with hormone-naive prostate cancer, 92.5% experienced an 80% or greater decline in prostate-specific antigen (PSA) levels after 25 weeks of treatment with enzalutamide, indicating strong efficacy in disease suppression.

Enzalutamide was generally well tolerated, with most side effects being mild to moderate, although some patients experienced grade 3 adverse events like pneumonia and hypertension, which were not deemed treatment-related.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study. Tombal, B., Borre, M., Rathenborg, P., et al.[2021]

In a study of 67 men with hormone-naive prostate cancer, 92.5% experienced an 80% or greater decline in prostate-specific antigen (PSA) levels after 25 weeks of treatment with enzalutamide, indicating strong efficacy in disease suppression.

Enzalutamide was generally well tolerated, with most side effects being mild to moderate, although some patients experienced grade 3 adverse events like pneumonia and hypertension, which were not deemed treatment-related.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Commentary on: "Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study." Tombal B, Borre M, Rathenborg P, Werbrouck P, Van Poppel H, Heidenreich A, Iversen P, Braeckman J, Heracek J, Baskin-Bey E, Ouatas T, Perabo F, Phung D, Hirmand M, Smith MR. Institut de Recherche Clinique, Université Catholique de Louvain, Brussels, Belgium. Electronic address: [e-mail]. Aarhus University Hospital, Aarhus, Denmark. Herlev Hospital, Herlev, Denmark. AZ Groeninge Kortrijk, Kortrijk, Belgium. UZ Leuven, Leuven, Belgium. Klinik und Poliklinik für Urologie, RWTH University Aachen, Aachen, Germany. Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. UZ Brussel, Brussels, Belgium. Univerzita Karlova v Praze, Prague, Czech Republic. Astellas Pharma Global Development, Leiden, Netherlands. Astellas Pharma Global Development, Northbrook, IL, USA. Medivation Inc, San Francisco, CA, USA. Massachusetts General Hospital Cancer Center, Boston, MA, USA: Lancet Oncol. 2014 May;15(6):592-600; doi: 10.1016/S1470-2045(14)70129-9. [Epub 2014 Apr 14]. Trump, D.[2018]

The combination of docetaxel and enzalutamide is feasible for treating metastatic castration-resistant prostate cancer (mCRPC), with 22 patients showing significant reductions in prostate-specific antigen levels, indicating potential efficacy.

However, the treatment was associated with higher-than-expected rates of neutropenia and fatigue, suggesting that while the combination is tolerable, careful monitoring for these side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Enzalutamide in Combination with Docetaxel in Men with Metastatic Castration-Resistant Prostate Cancer. Morris, MJ., Rathkopf, DE., Novotny, W., et al.[2021]

References

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

Docetaxel (Taxotere) and estramustine versus mitoxantrone and prednisone for hormone-refractory prostate cancer: scientific basis and design of Southwest Oncology Group Study 9916. [2018]

2. 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]

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. 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]

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

Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. [2021]

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study. [2021]

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

A phase I clinical study of high dose ketoconazole plus weekly docetaxel for metastatic castration resistant prostate cancer. [2021]

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

Commentary on: "Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study." Tombal B, Borre M, Rathenborg P, Werbrouck P, Van Poppel H, Heidenreich A, Iversen P, Braeckman J, Heracek J, Baskin-Bey E, Ouatas T, Perabo F, Phung D, Hirmand M, Smith MR. Institut de Recherche Clinique, Université Catholique de Louvain, Brussels, Belgium. Electronic address: [e-mail]. Aarhus University Hospital, Aarhus, Denmark. Herlev Hospital, Herlev, Denmark. AZ Groeninge Kortrijk, Kortrijk, Belgium. UZ Leuven, Leuven, Belgium. Klinik und Poliklinik für Urologie, RWTH University Aachen, Aachen, Germany. Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. UZ Brussel, Brussels, Belgium. Univerzita Karlova v Praze, Prague, Czech Republic. Astellas Pharma Global Development, Leiden, Netherlands. Astellas Pharma Global Development, Northbrook, IL, USA. Medivation Inc, San Francisco, CA, USA. Massachusetts General Hospital Cancer Center, Boston, MA, USA: Lancet Oncol. 2014 May;15(6):592-600; doi: 10.1016/S1470-2045(14)70129-9. [Epub 2014 Apr 14]. [2018]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Chemotherapy in hormone-sensitive metastatic prostate cancer: Evidences and uncertainties from the literature. [2022]

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

Phase Ib Study of Enzalutamide in Combination with Docetaxel in Men with Metastatic Castration-Resistant Prostate Cancer. [2021]

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

Quality of Life During Treatment With Chemohormonal Therapy: Analysis of E3805 Chemohormonal Androgen Ablation Randomized Trial in Prostate Cancer. [2022]