Enzalutamide + Cabazitaxel for Prostate Cancer

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: OHSU Knight Cancer Institute

Must be taking: LHRH agonist/antagonist

Must not be taking: Enzalutamide, Cabazitaxel

Disqualifiers: Seizure history, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 18-30 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining two drugs, cabazitaxel and enzalutamide, can more effectively treat prostate cancer that has spread and no longer responds to hormone treatments. Cabazitaxel stops cancer cells from growing and spreading, while enzalutamide blocks the hormones that help these cancer cells grow. The study seeks men with metastatic prostate cancer that has stopped responding to hormone therapy and who have shown signs of cancer progression, such as new symptoms or changes in test results. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Do I need to stop my current medications to join the trial?

Yes, you may need to stop certain medications before joining the trial. There is a required 'washout period' (time without taking certain medications) for androgen receptor antagonists, 5 alpha reductase inhibitors, or ketoconazole before starting the trial. If you are taking any of these, you will need to stop them for a specific time before the trial begins.

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

Research has shown that the combination of cabazitaxel and enzalutamide has been tested in previous studies. In one study, 56.3% of patients taking cabazitaxel experienced serious side effects. Similarly, about 52.4% of patients using an androgen-signaling–targeted inhibitor, like enzalutamide, also had serious side effects. Another study found that serious side effects were more common with cabazitaxel, affecting 65.4% of patients, compared to 30.2% for similar drugs.

These numbers indicate that while the combination can be effective, there is a significant risk of serious side effects. Prospective participants should consider this risk when thinking about joining a trial. A doctor can help explain the benefits and risks based on individual health. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining enzalutamide and cabazitaxel for prostate cancer because this duo could offer a powerful one-two punch against the disease. Enzalutamide works by blocking the action of male hormones that can fuel cancer growth, while cabazitaxel disrupts the division of cancer cells. This combination could potentially enhance effectiveness compared to current treatments like androgen deprivation therapy alone. Additionally, the use of cabazitaxel alongside enzalutamide might help overcome resistance that some patients develop to existing therapies, offering new hope for those with advanced prostate cancer.

What evidence suggests that this trial's treatments could be effective for metastatic, hormone-resistant prostate cancer?

Research has shown that using cabazitaxel and enzalutamide together, as studied in this trial, may help treat advanced prostate cancer that doesn't respond to hormone therapy. Cabazitaxel, a type of chemotherapy, has been proven to extend life and slow cancer progression when hormone treatments fail. One important study found that cabazitaxel outperformed other hormone treatments, such as abiraterone or enzalutamide alone. Another study demonstrated that cabazitaxel reduced the risk of death, helping patients live longer. Enzalutamide blocks male hormones that promote prostate cancer growth, making it a potentially strong partner with cabazitaxel for treating this challenging cancer. Together, these drugs offer hope for patients whose cancer hasn't responded to other treatments. ^{2 3 4 6 7}

Who Is on the Research Team?

Julie N Graff

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

This trial is for men with metastatic, hormone-resistant prostate cancer. Participants must have a good performance status (able to carry out daily activities), adequate blood counts and organ function, agree to use double barrier contraception, and be willing to provide a tumor sample if possible. Men who've had certain treatments or have specific health conditions are excluded.

Inclusion Criteria

My testosterone levels are low due to treatment or surgery.

I agree to provide a tumor sample if it's safe and possible, or I have an existing sample.

My prostate cancer is getting worse, shown by tests or symptoms.

Exclusion Criteria

I have never taken enzalutamide or ARN-509.

I have a history of seizures or conditions that could lead to seizures.

I haven't taken any experimental drugs in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive cabazitaxel IV over 1 hour on day 1 and enzalutamide PO QD on days 1-21 (days 2-21 of cycle 1). Cycles repeat every 21 days for 6-10 cycles.

18-30 weeks

1 visit every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit at 28 days post-treatment

Long-term Follow-up

Patients are followed up every 6 months for up to 5 years to assess overall survival and long-term outcomes.

Up to 5 years

1 visit every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cabazitaxel
• Enzalutamide

Trial Overview The study tests the combination of cabazitaxel (a chemotherapy drug) and enzalutamide (a hormone therapy) on patients with advanced prostate cancer that's spread and doesn't respond to hormonal treatment anymore. The phase I/II trial aims to find the best dose of cabazitaxel when used with enzalutamide.

How Is the Trial Designed?

Group I: Treatment (cabazitaxel, enzalutamide) Experimental Treatment 5 Interventions

Patients receive cabazitaxel IV over 1 hour on day 1 and enzalutamide PO QD on days 1-21 (days 2-21 of cycle 1). Patients also receive prednisone PO BID as standard of care with cabazitaxel. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue enzalutamide PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Jevtana for:

• Hormone refractory metastatic prostate cancer

Approved in United States as Jevtana for:

• Metastatic castration-resistant prostate cancer

Approved in Canada as Jevtana for:

• Hormone-refractory metastatic prostate cancer

Approved in Japan as Jevtana for:

• Prostate cancer

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

Cabazitaxel significantly improves overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC) compared to mitoxantrone, with a median survival of 15.1 months versus 12.7 months, indicating its efficacy as a treatment option.

The safety profile of cabazitaxel is similar to that of first-generation taxanes, with manageable side effects such as diarrhea and neutropenia, which can be addressed through monitoring and supportive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cabazitaxel--a next-generation taxane for the treatment of patients with metastatic castration-resistant prostate cancer]. Ecstein-Fraisse, E., Su, Z.[2014]

Enzalutamide is an effective androgen receptor inhibitor that improves overall survival in patients with metastatic castration-resistant prostate cancer, showing a 4.8-month survival benefit in those previously treated with docetaxel, as demonstrated in the Phase III AFFIRM trial.

The FDA has expanded enzalutamide's approval to include first-line treatment for metastatic castration-resistant prostate cancer in patients who have not yet received chemotherapy, and it is associated with an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide for patients with metastatic castration-resistant prostate cancer. Ramadan, WH., Kabbara, WK., Al Basiouni Al Masri, HS.[2020]

Cabazitaxel (Jevtana®) is an effective treatment for hormone-refractory metastatic prostate cancer, showing a 2.4-month increase in median overall survival and a 30% reduction in the risk of death compared to mitoxantrone, based on the main study for its EU approval.

The recommended dosage is 25 mg/m2 administered every 3 weeks via intravenous infusion, alongside daily oral prednisone, with common side effects including anemia and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency review of cabazitaxel (Jevtana®) for the treatment of hormone-refractory metastatic prostate cancer: summary of the scientific assessment of the committee for medicinal products for human use. Pean, E., Demolis, P., Moreau, A., et al.[2021]

Cabazitaxel, when combined with prednisone, significantly improves overall survival in patients with hormone-refractory metastatic prostate cancer who have previously been treated with docetaxel, as shown in the pivotal TROPIC trial.

The treatment also enhances progression-free survival and response rates for tumor and PSA levels, while maintaining an acceptable safety profile, with common side effects including hematological issues and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel: a guide to its use in hormone-refractory metastatic prostate cancer. Keating, GM.[2021]

Cabazitaxel, a new chemotherapy drug, has been shown to improve overall survival by 2.4 months in patients with metastatic castration-resistant prostate cancer who have progressed after docetaxel treatment, compared to the older drug mitoxantrone.

While cabazitaxel is effective, it carries a risk of significant hematologic toxicity, including febrile neutropenia, necessitating the use of hematopoietic growth factors in cases of severe neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cabazitaxel after docetaxel: a new option in metastatic castration-resistant prostate cancer]. Lheureux, S., Joly, F.[2018]

Cabazitaxel is a potentially effective treatment for castration-resistant prostate cancer (CRPC) in patients aged 80 years and older, showing similar efficacy in overall survival and PSA response rates compared to younger patients.

The safety profile of cabazitaxel is comparable across age groups, with high rates of adverse drug reactions (ADRs) in both patients aged <80 (77.2%) and ≥80 years (79.6%), primarily involving hematologic toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel in patients aged ≥80 years with castration-resistant prostate cancer: Results of a post-marketing surveillance study in Japan. Matsubara, N., Suzuki, K., Kazama, H., et al.[2021]

Cabazitaxel is an effective second-line treatment for men with metastatic castration-resistant prostate cancer (mCRPC), showing a median survival of 15.1 months compared to 12.7 months with mitoxantrone in a randomized trial.

While cabazitaxel has demonstrated efficacy, it is associated with significant adverse effects, including myelosuppression and febrile neutropenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel (jevtana): a novel agent for metastatic castration-resistant prostate cancer. Nightingale, G., Ryu, J.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1911206

Cabazitaxel versus Abiraterone or Enzalutamide in ... Cabazitaxel significantly improved a number of clinical outcomes, as compared with the androgen-signaling–targeted inhibitor (abiraterone or enzalutamide),

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11459482/

The Efficacy of Cabazitaxel in Treating Prostate Cancer Cabazitaxel achieved an HR of 0.77 (95% CI = [0.61, 0.97]) for PFS and 0.79 (95% CI = [0.70, 0.88]) for OS, indicating important improvements in ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2588931125001981

Cabazitaxel Versus Abiraterone or Enzalutamide for Poor- ... This study aims to compare the clinical efficacy of cabazitaxel versus ARPIs in patients with poor-prognosis mCRPC who have progressed on ...

4. pro.campus.sanofi pro.campus.sanofi/us/products/jevtana/efficacy-card-trial

JEVTANA ® (cabazitaxel) injection: CARD Trial - Efficacy & ... Kaplan-Meier curve: Median OS of 13.6 months with JEVTANA + prednisone, n. At the cutoff date, 153 deaths were noted, with 70 deaths (54.3 ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39153249/

Real-life Data on First- and Second-Line Treatment of ... Conclusion: These drugs have good efficacy in real-world evidence, similar to those reported in randomized clinical trials, with the expected exception of lower ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39987332/

Cabazitaxel versus abiraterone or enzalutamide for ... Results: Eight studies, comprising 1,897 patients were included, of whom 548 (28.8%) received cabazitaxel. Mean follow-up time ranged from 3 to ...

7. jevtana.com jevtana.com/study-results

See JEVTANA® (cabazitaxel) Injection Clinical Study Results JEVTANA was shown to be safe and effective in Study 3, that looked at the risk and benefits of two different dosing options in 1200 men: 20 mg/m2 versus 25 mg/m ...