FES Imaging + Tamoxifen for Breast Cancer

Recruiting at 1 trial location

Overseen By cancer connect

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Wisconsin, Madison

Must not be taking: ER blockers, QT prolongers

Disqualifiers: CNS metastases, Venous thrombosis, others

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: up to 6 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how to optimize tamoxifen treatment for individuals with a specific type of breast cancer that has spread. Researchers use a special imaging technique called FES-PET/CT (also known as 18F-Fluoroestradiol PET/CT or Cerianna) to assess how well tamoxifen blocks estrogen receptors in the cancer, particularly when a mutation reduces responsiveness to standard doses. The study aims to determine the best tamoxifen dose for those with an ESR1 mutation, a known cause of resistance to typical treatments. Suitable participants have metastatic breast cancer with this mutation and have previously received some form of endocrine therapy. As an Early Phase 1 trial, this research focuses on understanding tamoxifen's effects in people with this mutation, offering a chance to contribute to groundbreaking treatment insights.

Will I have to stop taking my current medications?

Participants must stop taking any ER blocking endocrine therapies like tamoxifen at least 60 days before the study. Additionally, medications that strongly affect certain liver enzymes (CYP2D6, CYP3A4, CYP2C9) are not allowed unless they can be stopped or switched to alternatives before starting the study.

What prior data suggests that FES-PET/CT imaging and tamoxifen are safe for use in this trial?

Research has shown that tamoxifen is widely studied and generally considered safe when used correctly. Many people have used it to treat and prevent breast cancer. Studies have found that taking tamoxifen for up to 10 years can lower the chance of breast cancer returning.

However, like any medication, tamoxifen can cause side effects. Common ones include hot flashes and a higher risk of blood clots. Despite these risks, the FDA has approved tamoxifen for treating breast cancer, indicating it has been tested for safety and effectiveness.

This trial tests different doses of tamoxifen, including higher doses than usual. While tamoxifen is usually well-tolerated at standard doses, higher doses might present different safety concerns. Participants should discuss any worries with the trial doctors, who will closely monitor for side effects and adjust treatment if needed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for breast cancer, which often includes chemotherapy and targeted therapies, this treatment combines tamoxifen with FES imaging. Tamoxifen is already known for blocking estrogen receptors, but this trial is exploring the potential of using FES-PET/CT scans to better monitor how well the drug is working. This approach could help tailor treatment to individual patients by providing real-time feedback on tamoxifen's effectiveness, potentially leading to more personalized and effective care. Researchers are excited because this could offer a more precise way to manage breast cancer treatment, improving outcomes by adjusting therapies based on how the cancer responds.

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

Research shows that tamoxifen effectively treats estrogen receptor-positive (ER-positive) breast cancer. Studies have found that women taking tamoxifen are about 75% more likely to remain disease-free compared to those who do not. Additionally, using tamoxifen for extended periods, such as 10 years, significantly reduces the risk of cancer recurrence. In this trial, participants will receive varying doses of tamoxifen to determine if dose adjustments can enhance effectiveness, especially for patients with specific genetic changes like ESR1. The aim is to find the optimal dose that effectively halts cancer growth while minimizing side effects. ^{1 4 5 6 7}

Who Is on the Research Team?

Kari B. Wisinski

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic or unresectable breast cancer that tests positive for estrogen receptor expression and has an ESR1 mutation. They must have had prior endocrine therapy, be stable after CNS metastases treatment, and able to take oral medications. Excluded are those with liver-only disease, recent other treatments, severe allergies to similar compounds as tamoxifen or FES-PET/CT components, certain health conditions, or concurrent malignancies.

Inclusion Criteria

I can take pills by mouth.

My cancer tests show at least 10% estrogen receptor presence.

My organs and bone marrow are functioning well.

Exclusion Criteria

I am aware that Tamoxifen can cause vaginal bleeding and harm to a fetus.

I do not have any unmanaged serious illnesses.

My nerve damage does not severely affect my daily activities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tamoxifen at varying dose levels, starting within 14 days of the FES-PET/CT scan, until there is evidence of progressive disease or drug intolerance

up to 6 weeks

Regular visits for FES-PET/CT imaging and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• FES PET/CT
• Tamoxifen

Trial Overview The study investigates the use of FES-PET/CT imaging to measure ERα blockade in order to find the optimal dose of tamoxifen for patients with ESR1 mutations. It's a pilot study aiming at improving dosing strategies by using advanced imaging techniques on participants who may not respond well to standard doses due to these specific gene mutations.

How Is the Trial Designed?

Group I: Tamoxifen Dose Levels Experimental Treatment 2 Interventions

Three participants will be enrolled to each dose level of oral tamoxifen (n = 12) Dose Level 1 = 20 mg daily Dose Level 2 = 80 mg daily Dose Level 3 = 160 mg daily Dose Level 4 = 200 mg daily Tamoxifen should be started within 14 days of the FES-PET/CT scan, at least 24 hours after FES injection. Participants will continue tamoxifen therapy until there is radiologic or clinical evidence of progressive disease or drug intolerance.

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

Approved in European Union as Nolvadex for:

• Breast cancer
• Infertility
• Gynecomastia

Approved in United States as Tamoxifen citrate for:

• Breast cancer
• Reduction in breast cancer incidence in high-risk women
• McCune-Albright Syndrome

Approved in Canada as Tamoxifen for:

• Breast cancer
• Reduction in breast cancer incidence in high-risk women

Approved in Japan as Tamoxifen for:

• Breast cancer

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Published Research Related to This Trial

Aromatase inhibitors, such as anastrozole and letrozole, show superior efficacy and a better safety profile compared to tamoxifen for treating metastatic breast cancer, making them a preferred option in first- and second-line treatments.

The ATAC trial indicates that anastrozole not only improves disease-free survival in hormone receptor-positive patients but also reduces the risk of developing contralateral breast cancer, highlighting its effectiveness in postmenopausal women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors in breast cancer: an update. Lake, DE., Hudis, C.[2018]

Tamoxifen citrate has been a crucial treatment for breast cancer over the past 25 years, significantly improving survival rates and reducing the risk of developing cancer in the other breast.

Patients appreciate the additional benefits of tamoxifen on cholesterol levels and bone health, but they also express concerns about potential side effects affecting their daily lives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamoxifen's impact on the management of breast cancer: patient perspectives. Reichman, BS.[2013]

Tamoxifen has been effectively used for over 30 years in treating various stages of breast cancer, including advanced and early cases, as well as for breast cancer prevention, demonstrating its broad applicability.

It is well-tolerated and effective in both pre- and postmenopausal women, making it the preferred hormonal treatment for patients with estrogen-receptor positive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamoxifen ("Nolvadex"): a review. Clemons, M., Danson, S., Howell, A.[2019]

Tamoxifen is widely used by 7 million women for breast cancer treatment and has been shown to significantly improve patient survival with minimal adverse effects.

While there is a slightly increased risk of endometrial cancer at the 20 mg/d dosage, this risk is considered minimal, and routine monitoring primarily involves clinical examinations rather than systematic endometrial testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Monitoring women on tamoxifen ]. Lansac, J., Diouf, A.[2013]

Tamoxifen is being evaluated in ongoing clinical trials involving over 24,000 healthy women to determine its effectiveness in preventing breast cancer, with results expected by the year 2000.

While tamoxifen may provide significant benefits in breast cancer prevention, it is associated with adverse effects such as transient bone loss in premenopausal women and potential uterine complications in postmenopausal women, leading to investigations of alternative drugs like raloxifene and toremifene.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Status of antiestrogen breast cancer prevention trials. Powles, TJ.[2016]

Aromatase inhibitors (AIs) like letrozole, anastrozole, and exemestane are now preferred over tamoxifen for treating hormone-receptor-positive early breast cancer in postmenopausal women, as they have shown greater effectiveness in preventing disease recurrence.

While AIs have a similar overall tolerability to tamoxifen, they present a lower risk of serious side effects such as endometrial cancer and thromboembolic events, although they may cause more arthralgia, myalgia, and bone loss, which can be managed with bisphosphonates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors in the adjuvant treatment of postmenopausal women with early breast cancer: Putting safety issues into perspective. Conte, P., Frassoldati, A.[2018]

Only 27.4% of surveyed primary care physicians prescribed tamoxifen for breast cancer prevention in the past year, indicating that its use is not widespread among these doctors.

Factors influencing the decision to prescribe tamoxifen included personal connections to breast cancer, patient inquiries about the drug, and the belief that its benefits outweigh the risks, while concerns about endometrial cancer risk had less impact on prescribing decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescription of tamoxifen for breast cancer prevention by primary care physicians. Armstrong, K., Quistberg, DA., Micco, E., et al.[2015]

In a study of 50 postmenopausal women with metastatic breast cancer who had not responded to previous treatments, tamoxifen citrate led to a complete remission in 8% and a partial remission in 28% of patients, with a median response duration of eight months.

Tamoxifen was found to significantly prolong survival in responders compared to nonresponders, and the side effects of the treatment were mild, making it a favorable option for patients after other therapies have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamoxifen. Use in treatment of metastatic breast cancer refractory to combination chemotherapy. Legha, SS., Buzdar, AU., Hortobagyi, GN., et al.[2019]

Molecular imaging with 16α-[18F]fluoro-17β-estradiol (FES) and 18F-fluoro-furanyl-norprogesterone PET can effectively evaluate the function of steroid hormone receptors in breast cancer, which is crucial for understanding treatment responses.

A current multicenter trial is underway to further validate FES-PET imaging, aiming to enhance its clinical application in predicting prognosis and personalizing endocrine therapy for patients with estrogen receptor-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Potential of Estrogen and Progesterone Receptor Imaging. Linden, HM., Peterson, LM., Fowler, AM.[2019]

Tamoxifen has been proven effective in improving recurrence-free and overall survival rates in breast cancer patients, making it the preferred long-term treatment for selected individuals.

While tamoxifen carries a small risk of developing endometrial cancer (approximately 2 per 1,000 women annually), most cases are detected early and are highly treatable, suggesting that the benefits of tamoxifen generally outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of tamoxifen on the endometrium. Barakat, RR.[2013]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK532905/

Tamoxifen - StatPearls - NCBI Bookshelf - NIH This drug is particularly effective for patients with estrogen receptor–positive tumors and is approved by the US Food and Drug Administration ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06154590?term=Tamoxifen&viewType=Table&rank=1

Study of Anastrozole Compared to NOLVADEX (Tamoxifen ... At a median follow-up of 33 months, the combination of anastrozole and NOLVADEX ( tamoxifen citrate ) did not demonstrate any efficacy benefit when compared ...

3. thelancet.com thelancet.com/journals/lanonc/article/PIIS0140-6736(12)61963-1/fulltext

Long-term effects of continuing adjuvant tamoxifen to 10 ... Thus, good evidence now exists that 10 years of tamoxifen in ER-positive disease produces substantial reductions in rates of recurrence and in breast cancer ...

4. frontiersin.org frontiersin.org/journals/oncology-reviews/articles/10.3389/or.2025.1564642/full

Treating ER-positive breast cancer: a review of the current ... The results demonstrated that women treated with tamoxifen had a 75% higher likelihood of remaining disease-free compared to those who received the placebo (79) ...

5. academic.oup.com academic.oup.com/jnci/article/90/18/1371/897928

Tamoxifen for Prevention of Breast Cancer: Report of the ... When related to the level of predicted risk among participants, the reduction of cancer risk ranged from 32% to 66%. Because the proportion of nonwhite women ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2005/17970s053lbl.pdf

NOLVADEX - (Tamoxifen Citrate) - accessdata.fda.gov Two European trials of tamoxifen to reduce the risk of breast cancer were conducted and showed no difference in the number of breast cancer ...

7. my.clevelandclinic.org my.clevelandclinic.org/health/treatments/9785-tamoxifen

Tamoxifen: Uses, Side Effects & Risks Research indicates that you're up to 61% more likely to experience breast cancer recurrence if you don't take tamoxifen at all or take it incorrectly. When To ...