Enzalutamide + Mifepristone or Chemotherapy for Breast Cancer

Recruiting at 13 trial locations

Overseen By Ayca Gucalp, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: CYP3A4 drugs, Corticosteroids

Disqualifiers: Seizure history, 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

Compensation: Varies

Number of Visits: 21

Duration: 21-day cycles, ongoing until disease progression

201 Participants Needed

Trial Summary

What is the purpose of this trial?

The researchers are doing this study to find out if the study drug, enzalutamide, alone or combined with the study drug, mifepristone, is effective in treating advanced or metastatic androgen receptor-positive (AR+) triple negative breast cancer (TNBC) or estrogen receptor-low breast cancer (ER-low BC), and whether these study treatments work as well as standard chemotherapy with carboplatin, paclitaxel, capecitabine, or eribulin.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot use certain medications that affect the CYP3A4 enzyme. You may need to switch to alternative medications if yours are strong inducers, inhibitors, or substrates of CYP3A4.

What data supports the effectiveness of the drugs used in the Enzalutamide + Mifepristone or Chemotherapy for Breast Cancer trial?

Research shows that capecitabine, a drug used in the trial, is effective and well-tolerated in treating metastatic breast cancer, and it may offer benefits when used early in the disease. Additionally, eribulin has been shown to improve survival in patients with previously treated metastatic breast cancer. ^{1 2 3 4 5}

Is Enzalutamide generally safe for humans?

Enzalutamide is generally well tolerated in humans, with most side effects being mild or moderate, but it carries a small increased risk of seizures and other side effects like hot flashes, high blood pressure, and fatigue. ^{6 7 8 9 10}

How is the drug combination of Enzalutamide and Mifepristone unique for breast cancer treatment?

This treatment is unique because it combines Enzalutamide, an androgen receptor blocker, with Mifepristone, which is known for its use in other conditions like abortion and Cushing's syndrome, to target breast cancer. This combination is novel as it explores the potential of androgen receptor inhibition in breast cancer, which is different from traditional chemotherapy approaches. ^{6 11 12 13 14}

Research Team

Tiffany Traina, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with advanced breast cancer that's spread and tests positive for certain receptors. They can have had one chemo treatment before, but not specific other treatments or conditions like brain metastases. Participants need to be able to take pills, have no severe diseases that could interfere, and agree to use two forms of birth control.

Inclusion Criteria

I can provide a breast cancer tissue sample for testing.

I have PD-L1 positive breast cancer and was treated with pembrolizumab and chemotherapy, unless I couldn't tolerate checkpoint inhibitors.

I am taking bisphosphonate or denosumab.

Exclusion Criteria

Pregnant patients

I have had seizures or conditions that could lead to seizures.

I have had cancer spread to my brain or its coverings.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either enzalutamide, enzalutamide with mifepristone, or chemotherapy in a 21-day cycle

21-day cycles, ongoing until disease progression

Visits every 21 days for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Crossover

Participants on chemotherapy may crossover to enzalutamide plus mifepristone upon disease progression

Treatment Details

Interventions

• Enzalutamide
• Mifepristone
• TPC

Trial Overview The study compares the effectiveness of Enzalutamide alone or combined with Mifepristone against standard chemotherapies (carboplatin, paclitaxel, capecitabine, eribulin) in treating advanced receptor-positive breast cancers. It aims to determine which method works best.

Participant Groups

Group I: Enzalutamide with Mifepristone Experimental Treatment 2 Interventions

Enzalutamide 120mg/day and mifepristone 300mg/day, continuous daily dosing in a 21-day cycle

Group II: Enzalutamide Experimental Treatment 1 Intervention

Enzalutamide 160 mg/day, continuous daily dosing in a 21-day cycle

Group III: Chemotherapy:Carboplatin, Paclitaxel, Eribulin or Capecitabine (TPC) Active Control 1 Intervention

The treating physician must select from one of the following regimens. * Eribulin 1.4 mg/m2 IV Day 1 and Day 8 in a 21-day cycle * Capecitabine 1000-1250 mg/m2 twice daily, orally Day 1-14 in a 21-day cycle * Paclitaxel 80 mg/m2 IV Day 1, Day 8 in a 21-day cycle * Carboplatin AUC 6 IV Day 1 in a 21-day cycle * Carboplatin AUC 2 IV Day 1, Day 8 and Day 15 in a 21-day cycle Patients randomized to TPC may be offered crossover to enzalutamide plus mifepristone treatment at the time of disease progression if they continue to meet eligibility criteria.

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

Approved in United States as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in European Union as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Canada as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Japan as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Corcept Therapeutics

Industry Sponsor

Trials

72

Recruited

7,700+

Dr. Joseph K. Belanoff

Corcept Therapeutics

Chief Executive Officer since 2014

MD from Stanford University

Dr. William Guyer

Corcept Therapeutics

Chief Medical Officer since 2021

PharmD

Astellas Pharma US, Inc.

Industry Sponsor

Trials

90

Recruited

12,900+

Naoki Okamura

Astellas Pharma US, Inc.

Chief Executive Officer since 2023

Not available

Tadaaki Taniguchi

Astellas Pharma US, Inc.

Chief Medical Officer since 2023

MD, PhD

Breast Cancer Research Foundation

Collaborator

Trials

79

Recruited

40,500+

Findings from Research

Capecitabine is a well-tolerated treatment for metastatic breast cancer, showing minimal side effects like myelosuppression and hair loss, which makes it a promising option for combination therapies with other anticancer drugs.

Ongoing phase II/III trials are investigating the use of capecitabine in early breast cancer treatment, and preliminary results indicate that it may provide significant benefits when used as part of adjuvant and neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future options with capecitabine (Xeloda) in (neo)adjuvant treatment of breast cancer. Fumoleau, P., Cameron, D.[2019]

The combination of eribulin and cyclophosphamide showed a clinical benefit rate of 79.5% in 44 patients with advanced breast cancer, indicating it is an effective treatment option for heavily pretreated individuals.

While the treatment was generally well-tolerated, neutropenia was the most common severe side effect, affecting 47.7% of patients, highlighting the need for monitoring blood cell counts during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib/II study of eribulin in combination with cyclophosphamide in patients with advanced breast cancer. Gumusay, O., Huppert, LA., Magbanua, MJM., et al.[2023]

In a study involving 58 patients with recurrent HER2-negative breast cancer, eribulin showed a median progression-free survival (PFS) of 6.6 months compared to 4.2 months for treatment of physician's choice (TPC), suggesting a potential benefit in delaying disease progression.

Although eribulin demonstrated improved median time to treatment failure (TTF) of 6.0 months versus 3.6 months for TPC, these differences were not statistically significant, indicating that further studies are necessary to confirm the efficacy of eribulin in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical usefulness of eribulin as first- or second-line chemotherapy for recurrent HER2-negative breast cancer: a randomized phase II study (JBCRG-19). Aogi, K., Watanabe, K., Kitada, M., et al.[2022]

In a phase II study involving 47 women with HER2-positive metastatic breast cancer, the combination of capecitabine, vinorelbine, and trastuzumab resulted in a confirmed response rate of 67%, exceeding the threshold needed to consider the treatment promising.

The treatment also showed a median progression-free survival of 11.3 months and a median overall survival of 28.5 months, indicating significant efficacy for patients receiving this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II interventional study (N0337) of capecitabine in combination with vinorelbine and trastuzumab for first- or second-line treatment of HER2-positive metastatic breast cancer: a north central cancer treatment group trial. Tan, WW., Allred, JB., Salim, M., et al.[2021]

In a phase 3 study, eribulin mesylate significantly improved overall survival in patients with previously treated metastatic breast cancer compared to the treatment of physician's choice.

Patients who had received three or fewer prior chemotherapy regimens experienced a longer median overall survival of 15.3 months with eribulin, compared to 13.2 months with control treatments, indicating that eribulin may be particularly effective in earlier lines of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of the number of prior chemotherapy regimens on outcomes for patients with metastatic breast cancer treated with eribulin: A post hoc pooled analysis. Cortes, J., Twelves, C.[2021]

In a phase III trial involving patients with metastatic, castration-resistant prostate cancer (mCRPC) who had progressed after docetaxel treatment, enzalutamide significantly improved overall survival, with a median survival of 18.4 months compared to 13.6 months for placebo, indicating a 37% reduction in mortality risk.

Enzalutamide was generally well tolerated, with most side effects being mild to moderate, although there is a small, dose-dependent risk of seizures; it also improved quality of life and pain management for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a review of its use in metastatic, castration-resistant prostate cancer. Sanford, M.[2021]

Enzalutamide, a common treatment for metastatic castration-resistant prostate cancer, can lead to serious skin reactions like Stevens-Johnson syndrome (SJS), as demonstrated in a case study where symptoms developed within two weeks of starting the medication.

Supportive care, including steroid treatment, was effective in resolving the skin lesions and improving symptoms within three weeks, highlighting the importance of monitoring patients closely for adverse effects early in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stevens-Johnson Syndrome Caused by Enzalutamide: A Case Report and Literature Review. Deng, M., Chai, H., Yang, M., et al.[2022]

A 76-year-old man developed severe thrombocytopenia after 13 days of enzalutamide treatment for castration-resistant prostate cancer, indicating that this side effect can occur early in therapy.

After discontinuing enzalutamide, the patient's platelet count recovered, and he was able to restart the medication without recurrence of thrombocytopenia; however, he later experienced a seizure, suggesting that enzalutamide may also be associated with neurological adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. Murata, M., Takizawa, I., Maruyama, R., et al.[2022]

In a phase III study involving men with progressive castration-resistant prostate cancer, enzalutamide significantly improved overall survival compared to placebo, with a median survival of 18.4 months versus 13.6 months.

Enzalutamide also showed benefits across all secondary endpoints, including a higher rate of prostate-specific antigen (PSA) decline and improved quality of life, although it was associated with common side effects like fatigue and diarrhea, and a rare incidence of seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a novel antiandrogen for patients with castrate-resistant prostate cancer. Hoffman-Censits, J., Kelly, WK.[2021]

Coadministration of the strong CYP2C8 inhibitor gemfibrozil significantly increases the exposure of enzalutamide and its active metabolite by 2.2-fold, indicating a potential need for dose adjustment when these drugs are used together.

Enzalutamide acts as a moderate inducer of CYP2C9 and CYP2C19 and a strong inducer of CYP3A4, which can reduce the effectiveness of other medications metabolized by these enzymes, suggesting that caution is needed when prescribing enzalutamide alongside other drugs with narrow therapeutic indices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Drug Interaction Studies with Enzalutamide. Gibbons, JA., de Vries, M., Krauwinkel, W., et al.[2021]

In the PREVAIL trial, enzalutamide significantly improved both radiographic progression-free survival and overall survival in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (CRPC), demonstrating its efficacy as a treatment option.

Enzalutamide was well tolerated and delayed the need for chemotherapy and decline in health-related quality of life, making it a convenient choice for patients who are asymptomatic or mildly symptomatic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a review of its use in chemotherapy-naïve metastatic castration-resistant prostate cancer. Keating, GM.[2021]

In a study of 61 men with metastatic castration-resistant prostate cancer (mCRPC) who progressed on abiraterone, both enzalutamide and docetaxel showed similar modest responses in prostate-specific antigen (PSA) levels and progression-free survival (PFS).

There were no significant differences in treatment outcomes between enzalutamide and docetaxel, suggesting that either drug could be a viable option for patients who have already been treated with abiraterone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical activity of enzalutamide versus docetaxel in men with castration-resistant prostate cancer progressing after abiraterone. Suzman, DL., Luber, B., Schweizer, MT., et al.[2021]

In a study of 35 patients with metastatic castration-resistant prostate cancer (mCRPC), enzalutamide showed a median overall survival of 7.5 months and a median progression-free survival of 3.1 months after prior treatment with taxane-based chemotherapy and abiraterone.

The most common side effects reported were anemia and weight loss, indicating that while enzalutamide has modest efficacy, it also carries risks that need to be managed in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide after docetaxel and abiraterone therapy in metastatic castration-resistant prostate cancer. Schmid, SC., Geith, A., Böker, A., et al.[2021]

An 82-year-old patient with chemotherapy-naive metastatic castration-resistant prostate cancer showed a long-term response to a very low dose of 40 mg enzalutamide daily, indicating that lower doses may still be effective.

Using lower doses of enzalutamide not only reduces the risk of side effects but could also lower healthcare costs and improve access to treatment, suggesting a need for further studies on the efficacy of these reduced doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep and ongoing response of castrate-resistant prostate cancer on very low-dose enzalutamide in an elderly chemotherapy-naïve patient: a case report. Boerrigter, E., Havenith, T., van Erp, NP., et al.[2021]

References

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

Future options with capecitabine (Xeloda) in (neo)adjuvant treatment of breast cancer. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

A phase Ib/II study of eribulin in combination with cyclophosphamide in patients with advanced breast cancer. [2023]

3. Japan pubmed.ncbi.nlm.nih.gov

Clinical usefulness of eribulin as first- or second-line chemotherapy for recurrent HER2-negative breast cancer: a randomized phase II study (JBCRG-19). [2022]

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

Phase II interventional study (N0337) of capecitabine in combination with vinorelbine and trastuzumab for first- or second-line treatment of HER2-positive metastatic breast cancer: a north central cancer treatment group trial. [2021]

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

Impact of the number of prior chemotherapy regimens on outcomes for patients with metastatic breast cancer treated with eribulin: A post hoc pooled analysis. [2021]

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

Enzalutamide: a review of its use in metastatic, castration-resistant prostate cancer. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Stevens-Johnson Syndrome Caused by Enzalutamide: A Case Report and Literature Review. [2022]

8. Australia pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. [2022]

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

Enzalutamide: a novel antiandrogen for patients with castrate-resistant prostate cancer. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Drug Interaction Studies with Enzalutamide. [2021]

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

Enzalutamide: a review of its use in chemotherapy-naïve metastatic castration-resistant prostate cancer. [2021]

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

Clinical activity of enzalutamide versus docetaxel in men with castration-resistant prostate cancer progressing after abiraterone. [2021]

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

Enzalutamide after docetaxel and abiraterone therapy in metastatic castration-resistant prostate cancer. [2021]

14. Germany pubmed.ncbi.nlm.nih.gov

Deep and ongoing response of castrate-resistant prostate cancer on very low-dose enzalutamide in an elderly chemotherapy-naïve patient: a case report. [2021]