Hormone Therapy +/− Everolimus for Breast Cancer

(e3 Trial)

Not currently recruiting at 1493 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: Southwest Oncology Group
Must be taking: Hormone therapy
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of hormone therapy in treating breast cancer, either alone or combined with everolimus, a targeted therapy. Hormone therapy aims to reduce estrogen levels, which can promote cancer growth, while everolimus may help stop tumor growth by blocking certain enzymes. The trial targets patients with hormone-receptor positive, HER2 negative breast cancer who have completed chemotherapy and surgery and are considered high-risk for cancer recurrence. Participants will receive either hormone therapy alone or with everolimus to determine which approach is more effective. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain drugs like strong CYP3A4 inhibitors or inducers during the study. It's best to discuss your current medications with the study team to see if any adjustments are needed.

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

Research has shown that the hormone therapies used in the trial, such as tamoxifen, anastrozole, and letrozole, are generally well-tolerated. These treatments have been used for many years to treat breast cancer, with common side effects including hot flashes and fatigue.

For everolimus, studies indicate it can also be effective, but it may cause a broader range of side effects. Some patients have experienced mouth sores or fatigue. Serious issues, like kidney problems, have been rare but have occurred in some cases. Despite these concerns, everolimus has demonstrated benefits in treating certain cancers, suggesting that its risks can be managed with proper care.

Overall, while hormone therapies usually have mild side effects, adding everolimus might increase the risks. However, the potential benefits in fighting cancer could make it worthwhile for some patients. It is important to consult a doctor to understand what these results mean for individual health.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment with everolimus for breast cancer because it targets a different mechanism compared to standard hormone therapies like tamoxifen or aromatase inhibitors. While most treatments focus on blocking hormone receptors or reducing estrogen production, everolimus works by inhibiting the mTOR pathway, which is involved in cell growth and proliferation. This dual approach could potentially enhance the effectiveness of existing hormone therapies and provide a new option for patients who have not responded well to standard treatments. The combination of hormone therapy with everolimus aims to delay disease progression more effectively than hormone therapy alone, offering hope for improved outcomes.

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

Research has shown that adding everolimus to hormone therapy can greatly improve outcomes for breast cancer patients. In this trial, participants in one arm will receive an approved endocrine therapy regimen along with everolimus. Studies have found that combining everolimus with hormone treatments like letrozole significantly extends the time before cancer worsens. Specifically, it more than doubles the time without tumor growth compared to hormone therapy alone and reduces the risk of cancer progression by 57%. Everolimus blocks certain enzymes in cancer cells, helping to stop their growth. This makes it a promising addition to hormone therapy for treating breast cancer.15678

Who Is on the Research Team?

MC

Mariana Chavez-MacGregor, MD, MSc

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for high-risk breast cancer patients who've had surgery with negative margins and appropriate axillary staging. They must have ER or PR positive status, not be on trastuzumab, have controlled diabetes if applicable, no uncontrolled lung disease, able to take oral meds, not pregnant/nursing, completed standard chemo prior to randomization, performance status 0-2 by Zubrod criteria. No recent heart attacks or severe cardiac disease.

Inclusion Criteria

I have more than one cancer spot in my breast, each far apart.
I have breast cancer in both breasts, diagnosed within a month of each other.
Patients must be high risk by belonging to one of the specified risk groups
See 24 more

Exclusion Criteria

My stomach and intestines work well and can absorb medication properly.
I do not have hepatitis.
I am not using, and will not use strong CYP3A4 inhibitors or inducers.
See 1 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an approved endocrine therapy for 2-5 years and either a placebo or everolimus for 1 year

2-5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years
Every 6 months for 2 years, then yearly

What Are the Treatments Tested in This Trial?

Interventions

  • Anastrozole
  • Everolimus
  • Exemestane
  • Goserelin Acetate
  • Letrozole
  • Leuprolide Acetate
  • Tamoxifen Citrate
Trial Overview The study tests hormone therapy's effectiveness against breast cancer when given alone versus alongside everolimus. Hormone therapies include tamoxifen citrate and others that lower estrogen levels in the body. Everolimus may inhibit tumor growth by blocking enzymes needed for cell growth.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Arm IIExperimental Treatment7 Interventions
Group II: Arm IPlacebo Group7 Interventions

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

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Approved in European Union as Arimidex for:
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Approved in United States as Arimidex for:
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Approved in Canada as Arimidex for:
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Approved in Japan as Arimidex for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Southwest Oncology Group

Lead Sponsor

Trials
389
Recruited
260,000+

SWOG Cancer Research Network

Lead Sponsor

Trials
403
Recruited
267,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Published Research Related to This Trial

Tamoxifen is the standard treatment for postmenopausal women with hormone-sensitive early breast cancer, but it has side effects that have led researchers to look for safer alternatives.
Third-generation aromatase inhibitors like anastrozole, letrozole, and exemestane have shown better efficacy and a more favorable side effect profile compared to tamoxifen in randomized trials.
Adjuvant aromatase inhibitor therapy for early breast cancer: A review of the most recent data.Grana, G.[2018]
Letrozole is an effective treatment for postmenopausal women with early-stage or advanced hormone-sensitive breast cancer, showing a 43% reduction in disease recurrences when used as extended adjuvant therapy beyond standard tamoxifen treatment.
In advanced breast cancer, letrozole outperformed tamoxifen in terms of time to disease progression (9.4 months vs. 6.0 months) and has a similar tolerability profile, making it a recommended first-line therapy according to treatment guidelines.
Letrozole: a review of its use in postmenopausal women with breast cancer.Simpson, D., Curran, MP., Perry, CM.[2018]
In a randomized trial, letrozole significantly improved disease-free survival by 19% and reduced the risk of breast cancer recurrence by 28% compared to tamoxifen in postmenopausal women with hormone receptor-positive early breast cancer.
Letrozole is considered cost-effective, providing an additional 0.343 quality-adjusted life years (QALYs) at an incremental cost of Can$ 8,110, resulting in a cost per QALY gained of Can$ 23,662 from the Canadian healthcare perspective.
Cost-effectiveness of letrozole versus tamoxifen as initial adjuvant therapy in postmenopausal women with hormone-receptor positive early breast cancer from a Canadian perspective.Delea, TE., El-Ouagari, K., Karnon, J., et al.[2022]

Citations

Long-Term Results with Everolimus in Advanced Hormone ...Using statistical methods fit for real-world data, our findings suggest that the use of everolimus may favorably impact overall survival, and ...
2.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/41022585/
Clinical outcomes of everolimus in patients with hormone ...Results: A total of 137 patients were included and the median progression-free survival (PFS) was 4.13 months (95% confidence interval [CI]: ...
Effectiveness of Adding Everolimus to ...In the present study, the addition of everolimus to letrozole resulted in a significantly longer median PFS in the intention-to-treat population ...
Everolimus in Postmenopausal Hormone-Receptor ...Everolimus combined with an aromatase inhibitor improved progression-free survival in patients with hormone-receptor–positive advanced breast cancer.
Novartis Drug Afinitor® Helps Women With Advanced ...Everolimus combined with hormonal therapy more than doubled time without tumor growth and reduced risk of progression by 57% vs hormonal therapy alone(1)-- ...
Efficacy and Safety of Everolimus in the Treatment ...Everolimus showed significant improvement in OS and PFS in patients with mBCa when compared to control. In addition, everolimus was associated with lower ...
Safety and efficacy of everolimus (EVE) plus exemestane ...Results. A total of 235 pts received EVE+EXE therapy. The overall safety analysis were similar to results previously reported for EVE+EXE. AEs were the main ...
AFINITOR (everolimus) tablets - accessdata.fda.govCases of renal failure (including acute renal failure), some with a fatal outcome, have been observed in patients treated with AFINITOR [see Laboratory Tests ...
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