Fulvestrant + Anastrozole for Breast Cancer

Not currently recruiting at 886 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

Must be taking: Anastrozole, Fulvestrant

Must not be taking: Hormone replacement

Disqualifiers: Premenopausal, Inflammatory breast cancer, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests treatments to determine which best shrinks breast cancer tumors before surgery. It compares anastrozole alone, fulvestrant alone, and a combination of both drugs. Anastrozole, a type of hormone therapy, lowers estrogen levels, while fulvestrant, also a hormone therapy, blocks estrogen receptors on tumor cells. Both aim to stop cancer growth. Postmenopausal women with estrogen receptor-positive breast cancer that can be felt or seen on imaging might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it does mention that hormone replacement therapy, megestrol acetate, or raloxifene should not be taken within one week before joining the study.

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

Previous studies have shown that patients tolerate anastrozole well, with long-term use significantly reducing breast cancer recurrence. The FDA has approved it for treating breast cancer after surgery. Research indicates that fulvestrant, although not approved for early-stage breast cancer, is effective and safe for advanced breast cancer, with no major safety concerns reported.

When used together, anastrozole and fulvestrant improve survival benefits compared to anastrozole alone. Serious side effects occurred at similar rates—17.1% for fulvestrant and 15.5% for anastrozole—indicating a comparable safety profile.

In summary, both anastrozole and fulvestrant, whether used separately or together, are generally well-tolerated with a similar rate of serious side effects. This suggests a promising safety profile for those considering participation in clinical trials with these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine or utilize well-known medications in potentially more effective ways. Fulvestrant and anastrozole are both established treatments for breast cancer, but this study is exploring their combination to see if it enhances efficacy. Anastrozole, an aromatase inhibitor, and fulvestrant, an estrogen receptor degrader, work together to block estrogen's effects on cancer cells. This combination could improve outcomes by attacking the cancer in two ways simultaneously, potentially offering a more robust approach than using either drug alone.

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

Research has shown that anastrozole, which participants in this trial may receive, helps shrink breast tumors by lowering estrogen levels. Studies have found it reduces the chance of the disease returning by 41% and lowers breast cancer-related deaths by 34%. Fulvestrant, another treatment option in this trial, works differently by decreasing the number of estrogen receptors in tumor cells and has effectively treated advanced breast cancer. Evidence from studies indicates that using fulvestrant with anastrozole, as tested in one of the trial arms, improves long-term survival compared to using anastrozole alone. This combination approach appears promising for enhancing treatment effectiveness in estrogen receptor-positive breast cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Cynthia Ma, MD, PhD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Postmenopausal women with Stage II-III estrogen receptor positive breast cancer, who have not started any treatment and are planning to undergo surgery. Participants must be at least 18 years old, have a specific score indicating the presence of estrogen receptors in their tumor cells, and meet certain health criteria based on blood tests and physical exams.

Inclusion Criteria

I am able to care for myself and perform daily activities.

My breast cancer is estrogen receptor positive with a high Allred score or high ER positivity.

Your recent lab test results need to meet certain standards.

Exclusion Criteria

I have not gone through menopause.

My breast cancer involves redness of the breast or skin invasion.

I have had a surgical biopsy for my breast cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Endocrine Treatment

Participants receive neoadjuvant endocrine therapy with either anastrozole, fulvestrant, or a combination of both for 24 weeks to shrink the tumor before surgery

24 weeks

Multiple visits for drug administration and monitoring

Surgery

Participants undergo surgery to remove the tumor after completing neoadjuvant endocrine therapy

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after surgery and treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Anastrozole
• Fulvestrant

Trial Overview The trial is testing whether taking fulvestrant alone or combined with anastrozole before surgery is more effective than just anastrozole for shrinking tumors. Anastrozole lowers estrogen to inhibit tumor growth and is standard care pre-surgery; fulvestrant decreases estrogen receptors in tumor cells but isn't approved for early-stage use yet.

How Is the Trial Designed?

Group I: Arm III (anastrozole and fulvestrant) Active Control 2 Interventions

Patients receive anastrozole daily in combination with fulvestrant on days 1 and 15 of cycle 1, and on day 1 of cycles 2-6 followed by surgery. A treatment cycle is 4 weeks in length. After completion of analysis of endocrine resistant data, patients will continue treatment as defined in the protocol.

Group II: Arm I (anastrozole) Active Control 1 Intervention

Patients receive anastrozole daily for 6 cycles followed by surgery. A treatment cycle is 4 weeks in length. After completion of analysis of endocrine resistant data, patients will continue treatment as defined in the protocol.

Group III: Arm II (fulvestrant) Active Control 1 Intervention

Patients receive fulvestrant on days 1 and 15 of cycle 1 and day 1 of cycles 2-6 followed by surgery. A treatment cycle is 4 weeks in length. After completion of analysis of endocrine resistant data, patients will continue treatment as defined in the protocol.

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

Approved in European Union as Arimidex for:

• Breast cancer
• Early breast cancer in postmenopausal women

Approved in United States as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

Approved in Canada as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• Treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Approved in Japan as Arimidex for:

• Breast cancer

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Anastrozole is a potent and selective third-line aromatase inhibitor that offers a significant advancement in the treatment of hormone-sensitive breast cancer, particularly for postmenopausal women.

This review highlights anastrozole's biochemical properties and clinical efficacy, indicating its widespread use as a first- and second-line treatment option, potentially providing better outcomes and safety compared to traditional therapies like tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer. Köberle, D., Thürlimann, B.[2018]

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 6241 postmenopausal women with early-stage breast cancer, anastrozole was found to have significantly fewer treatment-related adverse events compared to tamoxifen, indicating better tolerability.

Anastrozole also demonstrated a more favorable risk-benefit profile, with lower rates of serious adverse events and recurrence compared to tamoxifen, making it a preferable option for adjuvant treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Buzdar, A., Howell, A., Cuzick, J., et al.[2022]

Anastrozole is as effective as tamoxifen for treating advanced breast cancer in postmenopausal women, showing a slightly higher objective response rate (21% vs. 17%) and a significant clinical benefit in 59% of patients compared to 46% for tamoxifen.

Anastrozole offers a significant advantage in time to progression (median of 11.1 months vs. 5.6 months for tamoxifen) and has a lower incidence of side effects, such as thromboembolic events and vaginal bleeding, making it a preferable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. Nabholtz, JM., Buzdar, A., Pollak, M., et al.[2022]

In a retrospective analysis of the ATAC trial, women taking tamoxifen experienced significantly more gynecologic adverse events (34.2%) compared to those taking anastrozole (20.5%), leading to more medical interventions, including a nearly fourfold increase in hysterectomies.

The findings support the use of anastrozole as the preferred initial treatment for early hormone receptor-positive breast cancer due to its lower incidence of gynecologic complications, particularly since most adverse events with tamoxifen occurred within the first 2.5 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A lower incidence of gynecologic adverse events and interventions with anastrozole than with tamoxifen in the ATAC trial. Duffy, SR., Distler, W., Howell, A., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2690973/

Long-term efficacy and safety of anastrozole for adjuvant ... The results of the Oxford meta-analyses3,4 have demonstrated significant reduction in both disease recurrence (41%) and breast cancer specific mortality (34%) ...

2. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(19)32955-1/fulltext

Use of anastrozole for breast cancer prevention (IBIS-II) Two large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase ...

3. breastcancer.org breastcancer.org/research-news/10-years-arimidex

10 Years of Arimidex Reduces Recurrence Risk ... Taking Arimidex for 10 years after breast cancer surgery reduced recurrence risk, but didn't improve overall survival.

4. news.cancerresearchuk.org news.cancerresearchuk.org/2023/11/07/anastrozole-licensed-prevent-breast-cancer-high-risk-women/

Thousands of women offered anastrozole to help prevent ... Cases of invasive oestrogen receptor-positive breast cancer specifically were reduced by 54%, and ductal carcinoma in situ by 59%, especially in ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00994

Final Overall Survival in the Phase III FALCON Trial The randomized phase III FALCON trial demonstrated significant improvement in progression-free survival (PFS) with fulvestrant versus anastrozole in ...

6. breastcancer.org breastcancer.org/research-news/risk-reducing-effects-of-arimidex-last-years

Risk-Reducing Effects of Arimidex for High- ... The new results show that women who took Arimidex were 50% less likely to be diagnosed with breast cancer than women who didn't take Arimidex.

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK557856/

Aromatase Inhibitors - StatPearls - NCBI Bookshelf Anastrozole is a medication used in the management and treatment of breast cancer. It is in the aromatase inhibitors class of drugs.