Aromatase Inhibitor Therapy for Breast Cancer

(NAOMI Trial)

Not currently recruiting at 1 trial location

Overseen By Research Nurse

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Dartmouth-Hitchcock Medical Center

Must be taking: Aromatase inhibitors

Must not be taking: Endocrine therapy

Disqualifiers: Pregnancy, Lactation, 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)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 4-24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of letrozole, an aromatase inhibitor, in shrinking breast tumors before surgery in post-menopausal women. It focuses on women with estrogen receptor-positive (cancer grows in response to estrogen) and HER2-negative (a protein that promotes cancer growth is not present) breast cancer. Researchers will compare tumor samples taken before and after treatment to study the drug's effects on the cancer. The ideal participants are post-menopausal women diagnosed with Stage I-III breast cancer that requires surgery. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had any endocrine therapy for cancer in the last 10 years, and other neoadjuvant therapies for breast cancer are not allowed.

Is there any evidence suggesting that letrozole is likely to be safe for humans?

Earlier studies have shown that letrozole is a well-tolerated treatment option. Research indicates that this drug is associated with positive outcomes, including reduced risks of death from any cause and specifically from breast cancer.

One study found that letrozole improved overall survival rates compared to tamoxifen, another common breast cancer treatment. Women taking only letrozole had better survival rates over eight years.

While letrozole is generally safe, some side effects can occur, such as joint pain or hot flashes, which are common with this type of medication. However, serious problems are rare.

The FDA has already approved letrozole for treating certain types of breast cancer, supporting its safety. This approval means that previous research has deemed it safe enough for use in patients outside of clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Letrozole is unique because it is an aromatase inhibitor specifically designed to lower estrogen levels in the body, which is crucial for slowing down or stopping the growth of certain types of breast cancer. Unlike some standard treatments that might involve chemotherapy or radiation, letrozole directly targets and reduces the production of estrogen, a hormone that can fuel the growth of cancer cells. Researchers are excited about letrozole because it offers a highly targeted approach that can be effective in the pre-surgical setting, potentially allowing for a more precise and effective treatment plan with fewer side effects compared to more generalized cancer therapies.

What evidence suggests that letrozole might be an effective treatment for breast cancer?

Studies have shown that letrozole, the treatment being tested in this trial, effectively treats breast cancer. One study found that letrozole lowered the risk of recurrence, with 73.8% of women remaining cancer-free after 8 years. Another study demonstrated that letrozole significantly reduced breast cancer-related issues compared to those who did not take it. Letrozole blocks an enzyme called aromatase, which lowers estrogen levels and helps slow or stop the growth of certain breast tumors. These findings suggest letrozole can be a helpful treatment for post-menopausal women with specific types of breast cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Mary D. Chamberlin

Principal Investigator

Dartmouth-Hitchcock Medical Center

Are You a Good Fit for This Trial?

The NAOMI trial is for post-menopausal women over 18 with Stage I-III ER+ and HER2- breast cancer. Participants must have a tumor ≥1cm, not received prior endocrine therapy for any cancer, and meet specific blood criteria. Pregnant or lactating women are excluded.

Inclusion Criteria

Ability to give informed consent

Your blood tests show a normal level of white blood cells and platelets, and your liver function is within normal limits.

Your tumor must be at least 1 centimeter in size to provide enough tissue for testing.

Exclusion Criteria

Pregnant or lactating women

I have received hormone therapy for cancer.

I am receiving initial treatment for breast cancer, but I can take bisphosphonates for bone symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant letrozole therapy for 4 to 24 weeks prior to surgical resection of the tumor

4-24 weeks

Regular visits for treatment adherence and feedback

Surgery

Surgical resection of the tumor is performed after neoadjuvant therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments at 1 year and 3 years post-surgery

3 years

Periodic visits for assessments

What Are the Treatments Tested in This Trial?

Interventions

• Letrozole

Trial Overview

This study tests Letrozole as pre-surgery treatment in eligible women to see how the drug affects their breast tumors. It involves taking Letrozole for 4 to 12 weeks before surgery, with molecular analysis of tumor samples before and after treatment.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Letrozole 2.5mg tablet administered once daily for 4 to \~12 weeks (window of + 4 weeks for surgical scheduling flexibility) final dose taken the day of surgery.

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

Approved in United States as Femara for:

• Breast cancer in postmenopausal women
• Increasing the chance of ovulation in women with polycystic ovary syndrome

Approved in European Union as Letrozole for:

• Early breast cancer in postmenopausal women
• Advanced breast cancer in postmenopausal women

Approved in Canada as Letrozole for:

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

Who Is Running the Clinical Trial?

Dartmouth-Hitchcock Medical Center

Lead Sponsor

Trials

548

Recruited

2,545,000+

Published Research Related to This Trial

Aromatase inhibitors like anastrozole, letrozole, and exemestane are now the preferred hormonal treatments for estrogen-receptor-positive, postmenopausal metastatic breast cancer, replacing older therapies such as tamoxifen.

Recent studies have confirmed the effectiveness of these aromatase inhibitors in managing breast cancer, highlighting their critical role in targeting the hormonal pathways involved in the disease's progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonsteroidal and steroidal aromatase inhibitors in breast cancer. Hamilton, A., Volm, M.[2018]

Letrozole is a highly potent third-generation aromatase inhibitor that effectively blocks estrogen production, showing greater potency and selectivity compared to other aromatase inhibitors like anastrozole and exemestane.

Clinical trials have demonstrated that letrozole provides significant benefits for postmenopausal women with hormone-responsive breast cancer, outperforming the previous standard treatment, tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The discovery and mechanism of action of letrozole. Bhatnagar, AS.[2022]

In a study of 1065 postmenopausal women with early breast cancer receiving letrozole, immediate treatment with zoledronic acid significantly increased lumbar spine bone mineral density (BMD) by 5.7% compared to a delayed treatment strategy, which resulted in bone loss.

Both immediate and delayed zoledronic acid regimens were well tolerated, but the immediate group experienced more bone pain due to acute-phase reactions, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective inhibition of aromatase inhibitor-associated bone loss by zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: ZO-FAST Study results. Bundred, NJ., Campbell, ID., Davidson, N., et al.[2022]

In the BIG 1-98 trial, letrozole demonstrated a 19% reduction in the risk of disease-free survival events compared to tamoxifen, indicating its superior efficacy as an adjuvant therapy for early breast cancer.

Letrozole significantly reduced the risk of distant metastases (hazard ratio 0.73), establishing it as a standard treatment option for postmenopausal women with hormone-sensitive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of letrozole in the adjuvant setting: first results from the large, phase III, randomized trial BIG 1-98. Monnier, A.[2022]

In a study involving 8010 postmenopausal women with hormone-receptor-positive breast cancer, letrozole significantly improved disease-free survival compared to tamoxifen, with a 5-year survival rate of 84.0% versus 81.4%.

Letrozole reduced the risk of disease recurrence, particularly distant recurrence, by 19% compared to tamoxifen, although it was associated with a higher incidence of skeletal and cardiac events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. Thürlimann, B., Keshaviah, A., Coates, AS., et al.[2022]

Anastrozole and letrozole are effective oral treatments for advanced breast cancer in postmenopausal women, especially when other therapies like tamoxifen have not worked.

Both drugs are claimed to be more effective and less toxic than the standard treatment, megestrol acetate, although the review assesses the validity of these claims.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New aromatase inhibitors for breast cancer. [2019]

Letrozole is more effective than tamoxifen for adjuvant therapy in postmenopausal women with hormone-responsive early breast cancer, and it is well tolerated by patients.

Extended therapy with letrozole after tamoxifen treatment is more effective than placebo, making it a valuable treatment option while ongoing trials investigate the best duration and comparison with other aromatase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole: a review of its use in the treatment of postmenopausal women with hormone-responsive early breast cancer. Keating, GM.[2021]

In a study of 40 postmenopausal women with locally advanced breast cancer, both Letrozole and Tamoxifen were found to be effective as neoadjuvant hormone therapies, with 25% of patients on Tamoxifen and 20% on Letrozole not achieving a complete response, leading to subsequent radiotherapy.

The study indicated that neoadjuvant hormone therapy was generally well-tolerated, with side effects occurring in 55% of patients on Letrozole and 60% on Tamoxifen, suggesting that these treatments could improve clinical outcomes and allow for successful radical mastectomy in patients with better prognoses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Letrozole vs. tamoxifen as neoadjuvant therapy for postmenopausal patients with hormone-dependent locally-advanced breast cancer]. Novoa Vargas, A., Font López, KC., Amador, DD.[2018]

In a study of 3887 post-menopausal patients with hormone receptor-positive early breast cancer, over 85% persisted with letrozole treatment for 12 months, but 14.6% discontinued, primarily due to side effects.

Musculoskeletal symptoms and sleep disorders were the most significant adverse events leading to treatment discontinuation, with hazard ratios of 2.55 and 1.95, respectively, indicating a strong need for targeted compliance programs to support patients experiencing these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study. Nabieva, N., Fehm, T., Häberle, L., et al.[2022]

In a study involving 6182 postmenopausal women with hormone-receptor-positive breast cancer, sequential treatment with tamoxifen and letrozole did not significantly improve disease-free survival compared to letrozole monotherapy, indicating that letrozole alone may be sufficient for treatment.

The updated analysis showed no statistically significant difference in overall survival between letrozole and tamoxifen monotherapy, suggesting that both treatments have similar long-term outcomes, with adverse events consistent with previous reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. Mouridsen, H., Giobbie-Hurder, A., Goldhirsch, A., et al.[2022]

Letrozole is an effective and well-tolerated aromatase inhibitor used to treat metastatic breast cancer in postmenopausal women, with confirmed efficacy in both adjuvant and neoadjuvant settings based on clinical trials.

The review highlights the potential for future advancements in treatment by combining letrozole with new biologic agents and personalizing therapy through gene expression profiling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole. Dellapasqua, S., Colleoni, M.[2018]

Letrozole is a new non-steroidal aromatase inhibitor approved in Japan for treating postmenopausal women with breast cancer, particularly effective for those with steroid receptor positive or receptor-unknown locally advanced or metastatic cases.

The drug is generally well-tolerated, with mostly mild side effects such as hot flashes and fatigue, and has shown beneficial results in large international studies for post-surgical endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Introduction of new drug: letrozole, a new non-steroidal aromatase inhibitor for the treatment of postmenopausal women with breast cancer]. Tsukagoshi, S.[2018]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10637036/

Ten-year update: NRG Oncology/National Surgical ...

Letrozole statistically significantly reduced breast cancer–free interval events (HR = 0.75, 95% CI = 0.62 to 0.91; P = .003; absolute difference in cumulative ...

2.

drugs.com

drugs.com/medical-answers/success-rate-femara-breast-cancer-3546039/

What is the success rate for Femara in breast cancer?

In the BIG 1-98 trial, 73.8% of women who received letrozole alone had a disease-free survival at 8 years, compared to 70.4% of women who ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC2001225/

A decade of letrozole: FACE - PMC

Letrozole significantly reduced the risk of breast cancer recurrence (hazard ratio = 0.81; 95% confidence interval [CI] 0.70, 0.93; P = 0.003), especially the ...

4.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2016.69.2871

Comparative Efficacy and Safety of Adjuvant Letrozole ...

Letrozole did not demonstrate significantly superior efficacy or safety compared with anastrozole in postmenopausal patients with HR-positive, node-positive ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0748798311006986

High non-compliance in the use of letrozole after 2.5 years ...

31 patients (2.6%) had a recurrence and seven patients (0.6%) died over the follow-up period. Most patients (1069, 88%) started letrozole within six months of ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10853028/

Long-term Follow-up and Safety of Patients after an Upfront ...

We here report the primary efficacy and safety outcome of five years upfront therapy with letrozole. The therapy was indicated at the ...

7.

ascopubs.org

ascopubs.org/doi/abs/10.1200/JCO.2016.69.2871

Comparative Efficacy and Safety of Adjuvant Letrozole ...

The 5-year estimated overall survival rate was 89.9% for letrozole versus 89.2% for anastrozole arm (hazard ratio, 0.98; 95% CI, 0.82 to 1.17; P = .7916). Most ...

8.

ahajournals.org

ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044750

Aromatase Inhibitors and the Risk of Cardiovascular ...

These drugs have been associated with favorable clinical outcomes, including decreased risks of all-cause and breast cancer–related mortality, ...

9.

cancer.gov

cancer.gov/types/breast/research/letrozole-prevents-recurrence

Study Confirms Letrozole Prevents More Breast Cancer ...

Women who received letrozole alone also had better overall survival at 8 years than women receiving tamoxifen alone (83.4 versus 81.2 percent).

10.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00461773

Randomized Phase II Study of Preoperative Letrozole ...

The purpose of this study is to evaluate the objective response rate of a combination of letrozole (Femara) and bevacizumab (Avastin) given preoperatively ...