Fulvestrant + Enzalutamide for Breast Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining two treatments, fulvestrant and enzalutamide (both hormone therapies), for certain breast cancer patients compared to fulvestrant alone. It targets postmenopausal women with a specific type of breast cancer (ER+ Her2-) who plan to undergo surgery after about four months of treatment. Suitable candidates for this trial include women diagnosed with this type of breast cancer, who are not taking blood thinners, and are willing to participate in regular blood donations and biopsies for research. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that using fulvestrant with enzalutamide is generally safe for people. One study found that this combination caused only mild side effects, indicating they were not severe. Importantly, no new safety concerns emerged, suggesting that most patients can tolerate the treatment well.

Enzalutamide has undergone testing both alone and with other drugs in several studies. These studies support its use at a dose of 160 mg per day, demonstrating it can be safely combined with fulvestrant without altering the dose. This evidence reassures those considering this trial about the safety of the fulvestrant and enzalutamide combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Fulvestrant with Enzalutamide for breast cancer because it offers a new approach to treatment. While Fulvestrant is already used to block estrogen receptors in cancer cells, the addition of Enzalutamide, an androgen receptor inhibitor, introduces a novel mechanism by targeting androgen receptors. This dual approach could potentially improve outcomes by attacking the cancer through two hormonal pathways, which is different from the standard treatments that typically focus on estrogen alone. This combination could offer a promising new option for patients who have limited responses to existing therapies.

What evidence suggests that this trial's treatments could be effective for breast cancer?

This trial will compare the effectiveness of Fulvestrant alone versus Fulvestrant combined with Enzalutamide for treating certain types of breast cancer. Research has shown that combining Fulvestrant and Enzalutamide may be promising, with 25% of patients with ER+/HER2- breast cancer experiencing positive results from this combination after 24 weeks. Specifically, one in four patients benefited from the treatment at that time. Additionally, Fulvestrant alone is effective for advanced breast cancer and often yields results similar to anastrozole. This suggests that Fulvestrant, especially when combined with Enzalutamide, could be a valuable option for postmenopausal women with specific types of breast cancer. ^{1 3 4 6 7}

Who Is on the Research Team?

Anthony D Elias, M.D.

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10199936/

Phase II trial of fulvestrant plus enzalutamide in ER+/HER2 The primary efficacy endpoint of the trial was the clinical benefit rate at 24 weeks (CBR24). The median age was 61 years (46–87); PS 1 (0–1); ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04557449

NCT04557449 | Study to Test the Safety and Tolerability of ... This is a Phase 1/2A, open label, multicenter, nonrandomized, multiple dose, safety, tolerability, pharmacokinetic and pharmacodynamic study of PF-07220060

3. withpower.com withpower.com/trial/phase-3-breast-neoplasms-8-2017-1fe83

Fulvestrant + Enzalutamide 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, ...

4. onclive.com onclive.com/view/novel-cdk4-inhibitor-shows-activity-and-safety-in-hr-her2-metastatic-breast-cancer

Novel CDK4 Inhibitor Shows Activity and Safety in HR+ ... PF-07220060 plus endocrine therapy was tolerable and generated robust response rates in HR-positive, HER2-negative metastatic breast cancer.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37210417/

Phase II trial of fulvestrant plus enzalutamide in ER+/HER2 CBR24 was 25% (7/28 evaluable). Median progression-free survival (PFS) was 8 weeks (95% CI: 2-52). Adverse events were as expected for hormonal ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01597193

Safety Study of Enzalutamide (MDV3100) in Patients With ... The purpose of this study is to determine the safety, tolerability and pharmacokinetics of enzalutamide alone and in combination with anastrozole, or exemestane ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28280092/

A Phase I/Ib Study of Enzalutamide Alone and in Combination ... These results support a 160 mg/day enzalutamide dose in women with breast cancer. Enzalutamide can be given in combination with fulvestrant without dose ...