Fulvestrant + Enzalutamide for Breast Cancer

Recruiting at 2 trial locations

Overseen By Tiffany Colvin

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: Anti-androgens, Systemic estrogens

Disqualifiers: Brain metastases, Seizures, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 16 weeks

61 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic estrogens or androgens at least 14 days before starting the study treatment. Vaginal estrogens are allowed if needed for comfort.

What data supports the effectiveness of the drug Fulvestrant (Faslodex) for breast cancer?

Research shows that Fulvestrant is at least as effective as anastrozole, another breast cancer drug, in treating advanced breast cancer in postmenopausal women, providing a valuable option for those who have not responded to previous hormone therapies. ^{1 2 3 4 5}

Is the combination of Fulvestrant and Enzalutamide safe for humans?

Fulvestrant (Faslodex) is generally well tolerated in humans, with mild gastrointestinal symptoms being the most common side effect. It has been used safely in postmenopausal women with advanced breast cancer, even after other treatments have failed. ^{2 5 6 7 8}

How is the drug Fulvestrant + Enzalutamide unique for treating breast cancer?

Fulvestrant is unique because it is a selective estrogen receptor degrader (SERD) that targets and breaks down the estrogen receptor, unlike traditional treatments like tamoxifen, which can eventually lead to resistance. This makes it a promising option for advanced breast cancer, especially in postmenopausal women who have not responded to other endocrine therapies. ^{1 2 5 8 9}

What is the purpose of this trial?

This is a randomized two arm phase II study to further evaluate the efficacy of fulvestrant plus enza compared to single agent fulvestrant in postmenopausal women with locally advanced AR+/ER+/Her2- BC who will have local surgery after \~4 months on treatment.

Research Team

Anthony D Elias, M.D.

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

This trial is for postmenopausal women with advanced ER+/Her2- breast cancer who are planning surgery after treatment. Participants must be willing to donate blood and tissue, have no history of seizures or brain metastases, not use systemic estrogens/androgens (vaginal estrogens allowed), and meet certain health criteria like normal organ function tests.

Inclusion Criteria

Willing to donate blood for research at 4 time points

I am not taking blood thinners.

Your creatinine level should be less than 1.5 times the upper limit of normal.

Exclusion Criteria

I have been treated with medications targeting testosterone for my cancer.

I have not taken any systemic hormone treatments in the last 14 days, except for vaginal estrogens.

I have a history of seizures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fulvestrant with or without enzalutamide for approximately 4 months, with biopsies at 4 weeks and continued hormone therapy

16 weeks

Biopsy at 4 weeks, regular visits for hormone therapy

Surgical Resection

Participants undergo surgical resection after completion of hormone therapy

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including disease-free survival and PEPI score assessment

15 months

Long-term Follow-up

Participants are assessed for correlation between PEPI score and long-term outcomes such as disease-free survival and overall response rate

4 years

Treatment Details

Interventions

• Enzalutamide
• Fulvestrant

Trial Overview The study compares the effectiveness of two treatments: Fulvestrant alone versus Fulvestrant combined with Enzalutamide in patients before surgery. It's a phase II trial where participants are randomly assigned to one of the two groups to see which works better.

Participant Groups

Group I: Fulvestrant With Enzalutamide Experimental Treatment 2 Interventions

500 mg of Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC), plus160mg of Enzalutamide will be given daily.

Group II: Fulvestrant Without Enzalutamide Placebo Group 1 Intervention

500 mg of Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC)

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

Approved in European Union as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in United States as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Canada as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Japan as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

Fulvestrant (Faslodex) is as effective as anastrozole (Arimidex) for treating advanced breast cancer in postmenopausal women, with similar objective response rates across different patient subgroups.

Both treatments provided comparable clinical benefits, making fulvestrant a valuable option for patients with visceral metastases who have not responded to previous endocrine therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metastases: combined results from two multicentre trials. Mauriac, L., Pippen, JE., Quaresma Albano, J., et al.[2019]

In a study of 54 postmenopausal women with metastatic breast cancer, fulvestrant demonstrated clinical benefit in 38.9% of patients, with a median time to progression of 6.4 months, indicating its efficacy even after multiple prior treatments.

Fulvestrant was well tolerated, with no severe toxicities (grade 3/4) reported, suggesting it is a safe option for patients with advanced breast cancer who have limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex') in heavily pretreated postmenopausal patients with advanced breast cancer: single centre clinical experience from the compassionate use programme. Mlineritsch, B., Psenak, O., Mayer, P., et al.[2018]

In a study of 423 postmenopausal women with advanced breast cancer, those who progressed on fulvestrant still showed some sensitivity to subsequent endocrine therapies, with 54 patients experiencing clinical benefit from further treatment.

Fulvestrant can be an effective option in the treatment sequence for advanced breast cancer, potentially allowing patients to avoid cytotoxic chemotherapy longer by extending the use of endocrine therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmenopausal women who progress on fulvestrant ('Faslodex') remain sensitive to further endocrine therapy. Vergote, I., Robertson, JF., Kleeberg, U., et al.[2019]

Faslodex (fulvestrant) is a novel selective estrogen receptor down-regulator (SERD) that effectively targets and degrades the estrogen receptor, offering a new treatment option for advanced breast cancer, especially in cases where tumors have become resistant to tamoxifen.

Unlike tamoxifen, which can lead to resistance and has risks such as endometrial carcinoma, Faslodex provides a 'pure' antiestrogen effect without agonistic activity, making it a promising alternative for both advanced and early breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faslodex(TM) for the treatment of breast cancer. Smolnikar, K.[2019]

In a study involving 587 postmenopausal women with advanced breast cancer, fulvestrant showed similar efficacy to tamoxifen in patients with hormone receptor-positive tumors, with no significant differences in time to progression (TTP) or objective response rates.

While tamoxifen had a slightly better overall efficacy in the general population, both treatments were well tolerated, indicating that fulvestrant can be a viable option for patients with ER+ and/or PgR+ tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. Howell, A., Robertson, JF., Abram, P., et al.[2022]

Fulvestrant is a novel estrogen receptor antagonist used for the palliative treatment of advanced breast cancer in postmenopausal women, and it has no known agonist effects, making it a unique option for therapy.

The drug is well tolerated with mild gastrointestinal symptoms being the most common side effect, and it is administered as a once-a-month intramuscular injection, providing a convenient treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant antiestrogen for treatment of breast cancer. Hancock, CM.[2018]

In a study of 402 postmenopausal women with advanced breast cancer receiving fulvestrant through a Compassionate Use Program, 29.9% experienced clinical benefits, including partial responses and stable disease for over 6 months.

Fulvestrant was well tolerated, with only 1.5% of patients discontinuing treatment due to adverse events, indicating its safety and potential as an effective option for patients who have not responded to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) in advanced breast cancer: clinical experience from a Belgian cooperative study. Neven, P., Paridaens, R., Pelgrims, G., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metastases: combined results from two multicentre trials. [2019]

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

Fulvestrant ('Faslodex') in heavily pretreated postmenopausal patients with advanced breast cancer: single centre clinical experience from the compassionate use programme. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Postmenopausal women who progress on fulvestrant ('Faslodex') remain sensitive to further endocrine therapy. [2019]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex'): current and future role in breast cancer management. [2018]

5. Spain pubmed.ncbi.nlm.nih.gov

Faslodex(TM) for the treatment of breast cancer. [2019]

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

Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. [2022]

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

Fulvestrant antiestrogen for treatment of breast cancer. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) in advanced breast cancer: clinical experience from a Belgian cooperative study. [2018]

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

Fulvestrant: A Review in Advanced Breast Cancer Not Previously Treated with Endocrine Therapy. [2018]