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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with metastatic prostate cancer. Researchers aim to determine if adding enzalutamide (Xtandi) to the standard treatment of androgen deprivation therapy (ADT, or hormone therapy) and docetaxel is more effective and tolerable. Ideal participants have prostate cancer that has spread to other parts of the body and have not received certain previous treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that combining enzalutamide, docetaxel, and androgen deprivation therapy (ADT) is generally safe for treating advanced prostate cancer. Studies have found that this combination improves patient outcomes without causing unexpected safety issues.

For example, one study found that using enzalutamide and docetaxel together led to better results than using docetaxel alone, indicating the combination is both effective and manageable for patients. Another study showed that enzalutamide with ADT is well-tolerated by older patients with advanced prostate cancer.

Adding docetaxel to ADT has also been shown to extend patient survival. These positive findings suggest that the combination of enzalutamide, docetaxel, and ADT is safe, especially since enzalutamide is already approved for treating prostate cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about combining ADT, Docetaxel, and Enzalutamide for prostate cancer because this trio targets the disease from multiple angles. Androgen Deprivation Therapy (ADT) reduces the hormones that fuel cancer growth, Docetaxel is a chemotherapy drug that attacks rapidly dividing cancer cells, and Enzalutamide blocks the androgen receptor, further cutting off cancer’s fuel supply. Unlike standard treatments that usually involve ADT combined with just one additional drug, this combination offers a more comprehensive approach, potentially leading to more effective management of the disease. By integrating these three treatments, there's hope for improved outcomes and reduced progression of prostate cancer compared to existing options.

What evidence suggests that ADT + docetaxel + enzalutamide might be an effective treatment for metastatic prostate cancer?

Research has shown that combining hormone therapy (ADT) with the drugs docetaxel and enzalutamide may help treat prostate cancer that has spread. In this trial, participants will receive a combination of ADT, docetaxel, and enzalutamide. One study found that adding enzalutamide to docetaxel improved treatment results compared to using docetaxel alone. Additionally, using enzalutamide with hormone therapy has shown promise in lowering PSA levels, which doctors use to monitor prostate cancer. Starting treatment with six cycles of docetaxel and hormone therapy has also been linked to longer survival compared to hormone therapy alone. These findings suggest that using ADT, docetaxel, and enzalutamide together could be more effective for patients with advanced prostate cancer. ^{3 5 6 7 8}

Who Is on the Research Team?

Earle Burgess, MD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

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.

At least one PSA level of ≥ 5 ng/ml within 90 days prior to consent

Ability to understand and the willingness to sign a written informed consent document

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12394055/

Therapeutic outcomes of enzalutamide-docetaxel ... This study aimed to evaluate the therapeutic efficacy and adverse effects of combining enzalutamide with docetaxel versus using docetaxel alone ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.5072

Enzalutamide, docetaxel and androgen deprivation ... In this study, we hypothesized the combination of androgen deprivation therapy with Doc and enzalutamide (Enz) would improve the 52-week PSA CR rate.

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

Effectiveness of Adding Docetaxel to Androgen Deprivation ... ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer.

4. 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.

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

Which patients with metastatic hormone-sensitive prostate ... Adding docetaxel to androgen deprivation therapy (ADT) has been shown to improve survival in patients with metastatic, hormone-sensitive prostate cancer,.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39903972/

Enzalutamide and Docetaxel in Combination With ... ADT+Doc+Enz improved 52-week PSA CR compared to historical control with ADT+Doc. Achieving a PSA CR after 1 year of therapy correlated with improved OS.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1558767325000047

Enzalutamide and Docetaxel in Combination With ... Results of a randomized phase II trial demonstrated improved progression rates with the combination of enzalutamide and docetaxel compared to docetaxel alone.

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.5069

Clinical outcomes and safety of enzalutamide (ENZA) plus ... This post hoc analysis of ARCHES data demonstrated that ENZA + ADT provides clinical benefit and is generally well-tolerated in patients with mHSPC aged ≥75 ...