Enzalutamide + Cabazitaxel for Prostate Cancer

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

37 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I/II trial studies the side effects and best dose of cabazitaxel when given together with enzalutamide in treating patients with prostate cancer that has spread to other places in the body (metastatic) and has not responded to treatment with hormones or no longer responds to treatment with hormones (hormone-resistant). Drugs used in chemotherapy, such as cabazitaxel, 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. Androgen can cause the growth of prostate cancer cells. Hormone therapy using enzalutamide may fight prostate cancer by blocking the use of androgen by the tumor cells. Giving cabazitaxel together with enzalutamide may work better in treating metastatic, hormone-resistant prostate cancer.

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.

What data supports the effectiveness of the drug combination Enzalutamide + Cabazitaxel for prostate cancer?

Cabazitaxel has been shown to improve overall survival in patients with metastatic castration-resistant prostate cancer who have previously been treated with docetaxel, as demonstrated in the TROPIC trial. Enzalutamide is an androgen receptor-targeting agent used in similar conditions, suggesting potential effectiveness when combined with cabazitaxel. ^{1 2 3 4 5}

What safety information is available for Enzalutamide and Cabazitaxel in prostate cancer treatment?

Cabazitaxel and Enzalutamide have been studied for safety in treating prostate cancer. Common side effects of Cabazitaxel include low red and white blood cell counts and diarrhea. Enzalutamide is FDA-approved for prostate cancer, indicating it has been evaluated for safety. ^{1 2 6 7 8}

How is the drug combination of Enzalutamide and Cabazitaxel unique for prostate cancer treatment?

The combination of Enzalutamide and Cabazitaxel is unique because it targets prostate cancer that has become resistant to hormone therapy and previous chemotherapy with docetaxel. Cabazitaxel is a chemotherapy drug that works even when cancer cells have become resistant to other treatments, while Enzalutamide is a hormone therapy that blocks the effects of male hormones that can promote cancer growth. ^{1 2 3 4 9}

Research Team

Julie N Graff

Principal Investigator

OHSU Knight Cancer Institute

Eligibility Criteria

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

References

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

Cabazitaxel (jevtana): a novel agent for metastatic castration-resistant prostate cancer. [2023]

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

Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. France pubmed.ncbi.nlm.nih.gov

[Cabazitaxel after docetaxel: a new option in metastatic castration-resistant prostate cancer]. [2018]

5. Japan pubmed.ncbi.nlm.nih.gov

[Cabazitaxel--a next-generation taxane for the treatment of patients with metastatic castration-resistant prostate cancer]. [2014]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Enzalutamide for patients with metastatic castration-resistant prostate cancer. [2020]

7. England 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. [2021]

8. Netherlands 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. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Activity of cabazitaxel in castration-resistant prostate cancer progressing after docetaxel and next-generation endocrine agents. [2022]