Hormonal Therapy for Early-Stage Breast Cancer

Recruiting at 22 trial locations

Overseen By Kim Nelson, RN

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: QuantumLeap Healthcare Collaborative

Must be taking: Hormonal therapy

Disqualifiers: Pregnancy, Invasive carcinoma, Gastrointestinal disorders, others

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

Compensation: Varies

Number of Visits: 8

Duration: 6 months

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether monitoring and hormonal therapy can effectively manage ductal cell carcinoma in situ (DCIS), an early stage of breast cancer. Participants will receive either standard hormonal treatment or a new experimental treatment to determine which best controls the condition. Those diagnosed with DCIS who have recently had a mammogram and MRI might be suitable for this study. The trial includes regular check-ups with MRI scans and may involve providing blood, saliva, and tissue samples for further research. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking advancements in DCIS management.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, ongoing treatment for DCIS other than what is specified in this protocol is not allowed, so you may need to discuss your current medications with the trial team.

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

A previous study found that long-term treatment with testosterone and anastrozole did not increase cases of invasive breast cancer, suggesting this combination is generally safe. However, anastrozole alone can cause significant side effects due to reduced estrogen levels.

Research has shown that elacestrant, another drug in this trial, has side effects similar to standard hormone treatments, with no new or unexpected risks reported.

Studies have examined the side effects and optimal dosage of Z-endoxifen, the active component of tamoxifen, a drug already used to treat breast cancer. While some understanding of its safety exists, more specific information about Z-endoxifen is still being gathered.

Overall, the treatments in this trial have undergone safety testing in other studies. The trial phase indicates some evidence of their safety in humans. However, each participant's experience may vary, and ongoing monitoring remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for early-stage breast cancer because they offer new approaches that differ from the standard hormone therapies like tamoxifen and aromatase inhibitors (letrozole, anastrozole, exemestane). The Testosterone + Anastrazole combination is unique, as it involves subcutaneous pellets that release medication directly into the body over time, potentially offering more consistent blood levels of the drugs. Elacestrant stands out with its mechanism as a selective estrogen receptor degrader, lowering estrogen receptor activity in a novel way. Endoxifen, the active metabolite of tamoxifen, is explored for its potentially more direct and effective action against estrogen receptors. These treatments could offer new hope for patients who may not respond optimally to current options.

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

In this trial, participants will join different treatment arms to evaluate the effectiveness of various hormonal therapies for early-stage breast cancer. Previous studies have shown that women using a combination of testosterone and anastrozole, one of the treatments in this trial, experienced a significant reduction in breast cancer rates, more than three and a half times lower than expected. Anastrozole alone, also part of the trial, has effectively lowered estrogen levels, which is important for treating early-stage breast cancer. Research on elacestrant, another treatment option in this trial, has shown it significantly extended the time patients lived without their disease worsening, compared to standard treatments, for certain types of breast cancer. Lastly, (Z)-endoxifen, also being studied in this trial, has reduced breast density seen on mammograms, a risk factor for breast cancer, suggesting it might help slow down or stop tumor growth. These findings support the potential effectiveness of these treatments in managing early-stage breast cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Laura Esserman, MD, MBA

Principal Investigator

University of California, San Fancisco - Department of Surgery

(Co-PI) Kelly Hewitt, MD, FACS

Principal Investigator

Huntsman Cancer Institute at the University of Utah

Are You a Good Fit for This Trial?

This trial is for women aged 18 or older who have been diagnosed with an early stage of breast cancer known as HR+ DCIS, which is hormone receptor positive. They must be willing to provide tumor samples and consent to participate in the study.

Inclusion Criteria

My previous cancer was hormone receptor positive with a biopsy confirming it.

I am a woman and I am 18 years old or older.

You have the willingness and capability to provide tumor samples for research.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hormonal therapy and are evaluated with MRI at 3 and 6 months. Depending on the evaluation, they may continue treatment or undergo surgery.

6 months

3 visits (in-person) at baseline, 3 months, and 6 months

Follow-up

Participants are monitored with alternating MRI and mammogram every 6 months for up to 5 years, followed by annual follow-up for an additional 5 years.

10 years

Biannual visits (in-person) for 5 years, then annual visits

What Are the Treatments Tested in This Trial?

Interventions

• Anastrazole
• Elacestrant
• Exemestane
• Letrozole
• Tamoxifen
• Testosterone + Anastrazole
• Z-endoxifen

Trial Overview The RECAST Trial is testing whether active surveillance combined with hormonal therapy can effectively manage ductal cell carcinoma in situ (DCIS). Participants will receive either standard hormonal treatments or investigational drugs and undergo MRI evaluations.

How Is the Trial Designed?

Group I: Testosterone + Anastrazole (T+Ai) Experimental Treatment 1 Intervention

White solid pellet for subcutaneous insertion consisting of 100mg Testosterone and 4mg Anastrazole, an aromatase inhibitor. A cylindrical pellet (4.5mm diameter, 6.35mm diameter) is inserted subcutaneously in the upper outer gluteal region or iliac fossa every 3 months, with treatment up to 36 months. There is active follow up with MRI at baseline, 3 months, 6 months after treatment initiation, and every 6 months alternating MRI and mammogram for up to 5 years. Participants are followed for an additional 5 years.

Group II: Endoxifen Experimental Treatment 1 Intervention

(Z)-endoxifen is the most active metabolite of the selective estrogen receptor modulator (SERM), tamoxifen. Standard dose: 10mg PO delayed release capsule of z-endoxifen once daily for treatment up to 36 months. same time with a glass of water either 1 hour before a meal or 2 hours after a meal and should not take with alcohol. For patients on this arm there is active follow up with MRI at baseline, 3 months, 6 months after treatment initiation, and every 6 months alternating MRI and mammogram for up to 5 years. Participants are followed for an additional 5 years.

Group III: Elacestrant Experimental Treatment 1 Intervention

Selective estrogen receptor degrader, Standard dose: 400mg PO with food once daily for treatment up to 36 months. Dose reduction of Elacestrant by up to 2 dose levels permitted depending on toxicity; 400 mg to 300 mg then 300 mg to 200 mg Participants requiring more than 2 dose reductions must discontinue treatment For patients on this arm there is active follow up with MRI at baseline, 3 months, 6 months after treatment initiation, and every 6 months alternating MRI and mammogram for up to 5 years. Participants are followed by for an additional 5 years.

Group IV: chemoprevention therapy per investigator choice Active Control 4 Interventions

For premenopausal women: 20 mg tamoxifen orally daily (standard dose) or 10 mg every other day (low dose). For postmenopausal women: standard oral doses of AI of choice: exemestane 25 mg daily, letrozole 2.5 mg daily, or anastrozole 1 mg daily; or reduced exemestane dosing: 25 mg 3X per week orally. For postmenopausal women who are not tolerating an AI, investigators can change them to the low dose (10 mg every other day) or standard dose (20 mg) of tamoxifen. There is active follow up with MRI at baseline, 3 months, 6 months after treatment initiation, and every 6 months alternating MRI and mammogram for up to 5 years. Participants may continue treatment for up to 5 years.

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

Approved in European Union as Arimidex for:

• Early breast cancer
• Advanced breast cancer

Approved in United States as Arimidex for:

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

Approved in Japan as Arimidex for:

• Postmenopausal women with hormone receptor-positive early breast cancer
• Postmenopausal women with hormone receptor-positive recurrent breast cancer

Who Is Running the Clinical Trial?

QuantumLeap Healthcare Collaborative

Lead Sponsor

Trials

6

Recruited

7,000+

Published Research Related to This Trial

The FACE trial is a large-scale study involving 4000 postmenopausal women with hormone receptor-positive, node-positive breast cancer, comparing the efficacy and safety of letrozole and anastrozole over a treatment period of up to 5 years.

The primary goal of the trial is to assess disease-free survival (DFS), while secondary objectives include evaluating overall survival (OS) and the time to distant metastases, which will provide comprehensive insights into the effectiveness of both treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The FACE trial: letrozole or anastrozole as initial adjuvant therapy? Jonat, W., Mundhenke, C.[2018]

The ATAC trial is one of the few studies that directly compares aromatase inhibitors (AIs) for breast cancer treatment, providing valuable insights into their effectiveness.

Emerging evidence suggests a proposed sequence of hormonal therapies, including anastrozole and tamoxifen, tailored for different patient populations, which could optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hormonal therapy in early and advanced breast cancer. Buzdar, AU.[2019]

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant aromatase inhibitor therapy for early breast cancer: A review of the most recent data. Grana, G.[2018]

Aromatase inhibitors (AIs) like anastrozole, exemestane, and letrozole provide longer disease-free survival (DFS) compared to tamoxifen for women with early breast cancer, based on a review of multiple trials.

AIs are well tolerated and have a different safety profile than tamoxifen, making them a favorable option for initial adjuvant therapy or as a switch from tamoxifen after 2-3 years, especially for node-positive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choosing early adjuvant therapy for postmenopausal women with hormone-sensitive breast cancer: aromatase inhibitors versus tamoxifen. Carpenter, R.[2018]

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]

The ATAC trial, involving over 9,000 postmenopausal women, demonstrated that anastrozole significantly improves disease-free survival and reduces recurrence rates compared to tamoxifen, with benefits continuing even after treatment ends.

Anastrozole also has a favorable safety profile compared to tamoxifen, suggesting it may be a better initial treatment option for early breast cancer, especially when considering long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole as an adjuvant endocrine treatment for postmenopausal patients with breast cancer: emerging data. Buzdar, AU., Cuzick, J.[2018]

Anastrozole and letrozole significantly improve disease-free survival compared to tamoxifen in postmenopausal women with early-stage breast cancer, based on results from Phase III trials.

Switching to an aromatase inhibitor like anastrozole or exemestane after 2 to 3 years of tamoxifen therapy reduces the risk of cancer recurrence more effectively than continuing tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are all aromatase inhibitors the same? A review of controlled clinical trials in breast cancer. Berry, J.[2007]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole: a review of its use in postmenopausal women with breast cancer. Simpson, D., Curran, MP., Perry, CM.[2018]

Third-generation aromatase inhibitors (AIs) like anastrozole, letrozole, and exemestane have emerged as effective alternatives to tamoxifen for treating postmenopausal breast cancer, particularly in hormone receptor-positive cases, as shown in the ATAC trial with over five years of follow-up.

Fulvestrant, a new type of estrogen receptor antagonist with no partial agonist activity, represents a promising option in breast cancer treatment, and the review discusses future sequencing strategies for using AIs earlier in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the treatment of postmenopausal breast cancer. Howell, A.[2018]

Adjuvant hormonal therapy with tamoxifen significantly reduces the risk of breast cancer recurrence and death in women with early-stage, hormone receptor-positive breast cancer, but it also carries risks of endometrial cancer and thromboembolic events.

Recent trials, including the MA-17 and Intergroup Exemestane Study, show that selective aromatase inhibitors (AIs) like anastrozole and exemestane provide superior disease-free survival compared to tamoxifen, establishing AIs as a preferred treatment option for postmenopausal women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant aromatase inhibitors following tamoxifen for early-stage breast cancer in postmenopausal women: what do we really know? Chung, CT., Carlson, RW.[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]

Third-generation aromatase inhibitors, like anastrozole, letrozole, and exemestane, show significant antitumor activity in breast cancer treatment and have fewer side effects compared to tamoxifen.

Anastrozole has been found to be more effective than tamoxifen for postmenopausal women receiving adjuvant endocrine therapy, highlighting its potential as a preferred treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors in breast cancer therapy. Buzdar, AU.[2019]

Citations

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Real-world (RW) elacestrant use patterns and therapeutic ... In the EMERALD study, pts with ESR1-mutant (ESR1m) HR+/HER2-negative aBC had a median progression free survival (PFS) of 3.8 months (mos). Here, ...

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New Clinical Trial In Early-Stage Breast Cancer The study will evaluate whether elacestrant can delay the occurrence of metastasis or death compared to standard adjuvant endocrine therapy in ...

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