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

Trial Summary

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 data supports the effectiveness of the drug Tamoxifen for breast cancer?

Research shows that Tamoxifen is effective in treating metastatic breast cancer, with some patients experiencing complete or partial remission. It is also being studied for its potential to prevent breast cancer in healthy women, especially those at high risk. ^{1 2 3 4 5}

Is the combination of FES Imaging and Tamoxifen safe for humans?

Tamoxifen, used for breast cancer treatment, is generally safe but can have side effects like a small increased risk of endometrial cancer and other gynecological issues. Regular monitoring is recommended for those taking it long-term. ^{2 6 7 8 9}

How does the drug Tamoxifen differ from other breast cancer treatments?

Tamoxifen is unique because it acts as both an antiestrogen and an estrogen agonist, which can lead to different side effects compared to other treatments like aromatase inhibitors. It is effective in both pre- and postmenopausal women and is used not only for treatment but also for prevention of breast cancer in high-risk women. ^{2 4 6 9 10}

What is the purpose of this trial?

Despite broad advancements in endocrine therapy for ERα+ breast cancer, resistance ultimately develops. A common driver of resistance are known ESR1 mutations that lead to constitutively active receptor signaling and transcriptional regulation that is always "turned on" despite the absence of estrogen. Patients with ESR1 mutations are expected to have decreased binding affinity for tamoxifen and thus may be underdosed on standard therapy. \[18F\]-fluoroestradiol Positron Emission Tomography/Computed tomography (FES-PET/CT) imaging is a novel functional imaging technique that can non-invasively measure ERα expression and inhibition in metastatic ERα+ breast cancer. The proposed a pilot study uses FES-PET/CT imaging to measure ERα blockade to determine the optimal dose of tamoxifen in patients with ESR1 mutations.

Research Team

Kari B. Wisinski

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Tamoxifen. Use in treatment of metastatic breast cancer refractory to combination chemotherapy. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Status of antiestrogen breast cancer prevention trials. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Clinical Potential of Estrogen and Progesterone Receptor Imaging. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors in breast cancer: an update. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Prescription of tamoxifen for breast cancer prevention by primary care physicians. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. France pubmed.ncbi.nlm.nih.gov

[Monitoring women on tamoxifen ]. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

The effect of tamoxifen on the endometrium. [2013]

9. United States pubmed.ncbi.nlm.nih.gov

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

10. Netherlands pubmed.ncbi.nlm.nih.gov

Tamoxifen ("Nolvadex"): a review. [2019]