FES Imaging + Tamoxifen for Breast Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: University of Wisconsin, Madison
Must not be taking: ER blockers, QT prolongers
Disqualifiers: CNS metastases, Venous thrombosis, others
No Placebo Group
Approved in 5 Jurisdictions
Trial Summary
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.
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?
Is the combination of FES Imaging and Tamoxifen safe for humans?
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.246910
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.
See 10 more
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.
See 11 more
Trial 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 (Diagnostic Test)
- Tamoxifen (Selective Estrogen Receptor Modulator)
Trial OverviewThe 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
1Treatment groups
Experimental Treatment
Group I: Tamoxifen Dose LevelsExperimental Treatment2 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, Australia 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
🇦🇺 Approved in Australia as Tamoxifen for:
- Breast cancer
- Infertility
- Gynecomastia
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Wisconsin Carbone Cancer CenterMadison, WI
Wisconsin Oncology Network (WONIX) sitesMadison, WI
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Who Is Running the Clinical Trial?
University of Wisconsin, MadisonLead Sponsor
References
Tamoxifen. Use in treatment of metastatic breast cancer refractory to combination chemotherapy. [2019]Tamoxifen citrate (Nolvadex [Great Britain]; no comparable US product) is a recently developed antiestrogen with significant activity against metastatic breast cancer in postmenopausal women. We investigated its usefulness in breast cancer patients after conventional endocrine therapy and combination chemotherapy had failed. Of the 50 evaluable patients, four (8%) achieved a complete remission, 14 (28%) achieved a partial remission, and ten showed a less than partial response or stabilization of their disease. Median duration of response was eight months, and the survival of responders was significantly prolonged compared to that of the nonresponders. Side effects of the treatment were mild. These results demonstrate that tamoxifen offers the best choice of therapy for patients with metastatic breast cancer after conventional endocrine therapy and combination chemotherapy have failed.
Status of antiestrogen breast cancer prevention trials. [2016]Various ongoing double-blind clinical trials are evaluating the use of tamoxifen (Nolvadex) as chemoprevention for breast cancer. A total of over 24,000 healthy women have been randomized to these trials, and it should be possible, by the year 2000, to detect any preventive effect of tamoxifen in healthy women. Furthermore, with the large numbers of women involved, it should be possible to evaluate prevention in subgroups of participants according to risk of the disease, particularly those women carrying high-risk genes, such as BRCA1 and BRCA2. Adverse effects of tamoxifen have been identified, including a transient bone loss in premenopausal women and uterine effects, including polyps, cysts, and endometrial cancer, in postmenopausal women. Although the potential benefit of tamoxifen in preventing breast cancer in healthy women is likely to outweight any potential long-term risks, the use of other tamoxifen-like drugs, such as raloxifene (Evista) and toremifene (Fareston) is now being investigated.
Clinical Potential of Estrogen and Progesterone Receptor Imaging. [2019]Molecular imaging using 16α-[18F]fluoro-17β-estradiol (FES) and 18F-fluoro-furanyl-norprogesterone PET can assess in vivo function of steroid hormone receptors in breast cancer. These experimental agents have been tested in many single-center clinical trials and show promise to elucidate prognosis and predict endocrine therapy response. The current multicenter trial of FES-PET imaging will help bring this radiotracer closer to clinical use. There is tremendous potential for these tracers to advance drug development, enhance understanding of estrogen receptor-positive tumor biology, and personalize treatment.
Aromatase inhibitors in breast cancer: an update. [2018]Tamoxifen has been the endocrine treatment of choice for patients with breast cancer. The development of selective aromatase inhibitors has offered an alternative management approach for patients in whom a hormonal approach is indicated.
Prescription of tamoxifen for breast cancer prevention by primary care physicians. [2015]Although tamoxifen citrate has been approved for primary reduction of breast cancer risk since 1998, little is known about the prescription of tamoxifen by primary care physicians.
Aromatase inhibitors in the adjuvant treatment of postmenopausal women with early breast cancer: Putting safety issues into perspective. [2018]Tamoxifen has been the gold standard adjuvant therapy for the treatment of postmenopausal women with hormone-receptor-positive (HR+) early breast cancer for many years. Tamoxifen treatment is limited to 5 years because of the development of de novo and acquired resistance, and an ongoing risk of adverse events, including endometrial cancer, thromboembolic events, and gynecological symptoms with long-term use. The third-generation aromatase inhibitors (AIs), letrozole, anastrozole, and exemestane, are displacing tamoxifen as the first-choice therapy for HR+ early breast cancer, and are now recommended as the preferred therapy by national and international guidelines. Recent randomized trials have demonstrated that the AIs are more effective than tamoxifen in preventing disease recurrence when used in substitution and sequential strategies in the early adjuvant setting, and letrozole has been shown to be more effective than placebo in the extended adjuvant setting (after 5 years of tamoxifen therapy). Trial safety data show that the overall tolerability of AIs is similar to that of tamoxifen, with adverse events being predictably characteristic of estrogen deprivation; however, some important differences in adverse event profiles between tamoxifen and the AIs have been demonstrated. In addition to antiestrogenic effects, tamoxifen acts as an estrogen agonist in some tissues, which can lead to serious side effects not associated with the AIs, which prevent estrogen biosynthesis. A lower incidence of gynecological and thromboembolic events is observed in patients taking AIs, and fewer cases of endometrial cancer are seen compared with tamoxifen. Adverse events that are more frequent with adjuvant AI therapy compared with tamoxifen include arthralgia and myalgia, bone loss, and effects on the cardiovascular system and blood lipids. The effects of AIs on bone are predictable and may be easily managed, where necessary, with bisphosphonates. Studies examining the effects of AIs on the cardiovascular system and lipid profiles, including in the extended adjuvant setting, suggest that these adverse events may be due to the absence of a protective effect of tamoxifen rather than true AI toxicity. Further studies are required to determine the long-term safety of AI therapy in postmenopausal women with HR+ early breast cancer.
[Monitoring women on tamoxifen ]. [2013]Worldwide, 7 million women are taking tamoxifen for breast cancer. The beneficial effects of tamoxifen on patient survival have been clearly demonstrated. Tamoxifen has few adverse effects and severe complications are very uncommon. An higher risk of endometrial cancer at the 20 mg/d dosage has been discussed and if it does exist, is minimal (RR x 2 instead of 1.3). Patient monitoring is basically clinical with an annual examination of the lower limbs and genital organs and an ophthalmological examination. Further explorations are needed in cases with specific symptoms, especially metrorrhage. There has been no proof that systematic endometrial cytology or ultrasound explorations are useful.
The effect of tamoxifen on the endometrium. [2013]Tamoxifen (Nolvadex), a nonsteroidal antiestrogen, was first approved by the FDA for the treatment of patients with breast cancer in 1978. Large clinical trials have demonstrated a recurrence-free and overall survival benefit in both pre- and postmenopausal women. Long-term adjuvant tamoxifen is the endocrine treatment of choice for selected patients with breast cancer, and large-scale trials are currently underway to evaluate its role as a chemopreventive agent in healthy women at risk for breast cancer. Consequently, a large number of women will be subjected to both the benefits and potential risks of long-term tamoxifen therapy. One of the most significant potential complications is the development of endometrial cancer. The estimated annual risk of endometrial cancer in tamoxifen-treated patients is approximately 2 per 1,000 women. Most of these cancers will be detected at an early stage when they are highly curable. The potential benefit of tamoxifen treatment in breast cancer patients outweighs this risk; however, all patients receiving tamoxifen should undergo regular gynecologic evaluations.
Tamoxifen's impact on the management of breast cancer: patient perspectives. [2013]Tamoxifen citrate has been prescribed to millions of women with breast cancer and has been one of the most important advances in breast cancer treatment over the past 25 years. Because she is a female physician, the author's patients tend to be particularly open about their concerns regarding breast cancer and its treatment. Women accept tamoxifen as a treatment because of its demonstrated efficacy in breast cancer, extending survival and reducing contralateral breast cancer. They also recognize the potential benefits of secondary effects on lipids and bone. However, patients do have concerns regarding side effects and their impact on everyday life.
Tamoxifen ("Nolvadex"): a review. [2019]Tamoxifen has been used in the management of breast cancer for over 30 years. Since its introduction for the treatment of advanced breast cancer, its indications have increased to include the treatment of early breast cancer, ductal carcinoma in situ, and more recently for breast cancer chemoprevention. Tamoxifen has a good tolerability profile and moreover, unlike many other endocrine therapies, it is efficacious in both pre- and postmenopausal women. It is the combination of efficacy and tolerability that allows tamoxifen to maintain its position as the hormonal treatment of choice for most patients with oestrogen-receptor positive breast cancer. Ongoing studies will provide further information about the optimal duration of tamoxifen therapy and how it compares with the newer aromatase inhibitors.