Hormonal Therapy for Early-Stage Breast Cancer
Recruiting in Palo Alto (17 mi)
+7 other locations
Age: 18+
Sex: Female
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: QuantumLeap Healthcare Collaborative
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The goal of this trial is to see if active surveillance monitoring and hormonal therapy in patients diagnosed with ductal cell carcinoma in situ (DCIS), an early stage of breast cancer, can be an effective management of the disease.
Participants will be asked to receive control hormonal therapy or an investigational hormonal therapy treatment. Participants will be asked to return for evaluation with MRI at three months and six months. Depending on the evaluation participants will have the option to continue on the treatment. If the evaluation suggests surgery is recommended, the participant will discontinue the study treatment and will undergo surgery. In addition to the treatment and MRI evaluation, participants will be asked to provide blood sample to understand their immune status, provide saliva sample for genetic testing, provide the study with a portion of the tissue or slides generated from tissue removed during surgery performed as part of their standard of care.
Is the drug Anastrazole, Elacestrant, Exemestane, Letrozole, Tamoxifen, Testosterone + Anastrazole, Z-endoxifen promising for early-stage breast cancer?Yes, these drugs are promising for early-stage breast cancer. Anastrozole, letrozole, and exemestane, known as aromatase inhibitors, have shown to be effective and have fewer side effects compared to tamoxifen. Anastrozole, in particular, has been found to improve disease-free survival in postmenopausal women. These drugs are considered strong options for treating hormone receptor-positive breast cancer.23567
What safety data is available for hormonal therapy in early-stage breast cancer?The ATAC trial, which included over 9,000 postmenopausal women, compared the safety of anastrozole and tamoxifen as adjuvant treatments for early-stage breast cancer. The trial showed that anastrozole has a favorable safety profile compared to tamoxifen, with mature safety data confirming these findings at 68 months median follow-up. The FACE trial is also assessing the safety of letrozole versus anastrozole, with results pending. Overall, anastrozole, letrozole, and exemestane are considered effective and generally well-tolerated, though long-term safety profiles may differ among them.1681011
What data supports the idea that Hormonal Therapy for Early-Stage Breast Cancer is an effective treatment?The available research shows that hormonal therapy drugs like anastrozole, letrozole, and exemestane are more effective than tamoxifen for treating early-stage breast cancer in postmenopausal women. For example, letrozole improved disease-free survival and reduced the chance of cancer coming back by 43% compared to a placebo. These drugs also have better tolerability, meaning they cause fewer side effects, making them a preferred choice over tamoxifen.1491213
Do I have to stop taking 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.
Eligibility Criteria
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.
Participant Groups
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.
4Treatment groups
Experimental Treatment
Active Control
Group I: Testosterone + Anastrazole (T+Ai)Experimental Treatment1 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: EndoxifenExperimental Treatment1 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: ElacestrantExperimental Treatment1 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 choiceActive Control4 Interventions
a. For premenopausal women: 20 mg or 5 mg tamoxifen orally b. 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 3 times per week orally i. For postmenopausal women who are not tolerating an AI, low dose (5 mg) 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Berkeley Outpatient CenterBerkeley, CA
Bryn Mawr HospitalBryn Mawr, PA
Riddle HospitalMedia, PA
Paoli HospitalPaoli, PA
More Trial Locations
Loading ...
Who is running the clinical trial?
QuantumLeap Healthcare CollaborativeLead Sponsor
References
New aromatase inhibitors for breast cancer. [2019]Anastrozole (Arimidex-Zeneca) and letrozole (Femara-Novartis) are the first selective, oral, non-steroidal aromatase inhibitors. They are licensed for the treatment of advanced breast cancer in postmenopausal women where tamoxifen or other anti-oestrogen therapy has failed. The manufacturers of both drugs claim that their products are more effective, less toxic and better tolerated than the progestogen megestrol acetate, the standard therapy in this clinical situation. We assess these claims.
Aromatase inhibitors in breast cancer therapy. [2019]Recent advances have been made in the hormonal treatment of breast cancer with the advent of third-generation aromatase inhibitors (anastrozole, letrozole, and exemestane). These newer agents have substantial antitumor activity and appear to be as effective as tamoxifen, with fewer adverse effects. Recent reports indicate that anastrozole is more effective than tamoxifen as adjuvant endocrine therapy in postmenopausal women with breast cancer. This report provides an overview of the clinical trials conducted to date with the aromatase inhibitors as first- and second-line therapies, with an emphasis on recently updated analyses comparing anastrozole with tamoxifen in the adjuvant setting.
Hormonal therapy in early and advanced breast cancer. [2019]While some of the most intriguing data on the development of hormonal therapy for breast cancer have come from studies on aromatase inhibitors (AIs), few trials have compared these agents directly, with the exception of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial. Based on the latest results from this trial and on previous investigations of other AIs, a proposed sequence of hormonal therapies (including anastrozole, tamoxifen, letrozole, fulvestrant, and megestrol acetate) for the treatment of breast cancer is beginning to emerge for various patient populations.
Letrozole: a review of its use in postmenopausal women with breast cancer. [2018]Letrozole (Femara), a nonsteroidal, third-generation aromatase inhibitor administered orally once daily, has shown efficacy in the treatment of postmenopausal women with early-stage or advanced, hormone-sensitive breast cancer. In early-stage disease, extending adjuvant endocrine therapy with letrozole (beyond the standard 5-year period of tamoxifen) improved disease-free survival; compared with placebo there was a 43% relative reduction in disease recurrences or new contralateral breast tumours at a median follow-up of 2.4 years. The results of 4 months' neoadjuvant treatment with letrozole or tamoxifen in postmenopausal women with untreated primary disease favour letrozole. In advanced breast cancer, letrozole was superior to tamoxifen as first-line treatment; time to disease progression was significantly longer (9.4 vs 6.0 months, p
Adjuvant aromatase inhibitors following tamoxifen for early-stage breast cancer in postmenopausal women: what do we really know? [2019]Adjuvant hormonal therapy in the treatment of women with early-stage, hormone receptor (HR)-positive breast cancer is now considered the standard of care. Adjuvant tamoxifen decreases the risk of breast cancer recurrence and death in women with early-stage breast cancer when taken for 5 years. The benefits of tamoxifen are counterbalanced by toxicities including an increased risk of endometrial cancer and thromboembolic events. The selective aromatase inhibitors (AIs)--including anastrozole, letrozole, and exemestane--are challenging the role of tamoxifen as the adjuvant hormonal therapy of choice in postmenopausal women. Results of the Arimidex and Tamoxifen Alone or in Combination trial favor the use of anastrozole over tamoxifen as initial adjuvant hormonal therapy, with improvement in disease-free survival (DFS) and a favorable toxicity profile. The results of 2 large adjuvant trials using AIs sequentially with tamoxifen in postmenopausal women with early-stage, HR-positive breast cancer have been reported. The MA-17 study randomized women to placebo or letrozole for 5 years after completion of 4.5-6 years of initial tamoxifen. The Intergroup Exemestane Study (IES) randomized women following 2-3 years of adjuvant tamoxifen to continue to receive tamoxifen or switch to exemestane for a total of 5 years of adjuvant hormonal therapy. The MA-17 and IES trials demonstrated superior DFS with the AI and corroborated the smaller GROCTA-4B and Italian Tamoxifen Arimidex trials, which studied sequential therapy with aminoglutethamide or anastrozole. There is now substantial medical evidence supporting the use of AIs in postmenopausal women with early-stage, HR-positive breast cancer.
New developments in the treatment of postmenopausal breast cancer. [2018]In recent years, new agents have challenged tamoxifen as the standard endocrine therapy for postmenopausal breast cancer. This article reviews developments with regard to the third-generation aromatase inhibitors (AIs)--anastrozole, letrozole and exemestane--and fulvestrant, the first of a new type of estrogen receptor antagonist that, unlike tamoxifen, has no partial agonist activity. The final results of the "Arimidex", Tamoxifen, Alone or in Combination (ATAC) trial, at a median follow-up of more than five years, and recent results from switching studies with anastrozole and exemestane, strengthen the position of these AIs as adjuvant treatment for hormone receptor-positive early breast cancer. Sequencing options for the future are also discussed because non-steroidal AIs are increasingly used early in the treatment sequence.
Are all aromatase inhibitors the same? A review of controlled clinical trials in breast cancer. [2007]Five years of tamoxifen therapy has been the standard of care for the adjuvant treatment of estrogen receptor-positive early-stage breast cancer for many years and was the first hormonal treatment for postmenopausal women with advanced or metastatic disease. The third-generation aromatase inhibitors (AIs) anastrozole, exemestane, and letrozole offer new treatment options, although their efficacy has not been compared directly in randomized, double-blind, controlled trials in any breast cancer treatment setting.
Anastrozole as an adjuvant endocrine treatment for postmenopausal patients with breast cancer: emerging data. [2018]The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial compared the efficacy and safety of anastrozole versus tamoxifen versus the combination as initial adjuvant treatment for early breast cancer in over 9,000 postmenopausal women. Analyses at 33 and 47 months median follow-up showed that anastrozole significantly prolonged disease-free survival and time to recurrence and reduced the incidence of contralateral breast cancer compared with tamoxifen. Results of the completed treatment analysis at 68 months median follow-up confirmed the earlier findings, showing that the absolute difference in disease-free survival continued to increase beyond completion of treatment. Mature safety data from the ATAC trial show that, overall, anastrozole has a favorable safety profile compared with tamoxifen. In the absence of current data on further follow-up or the outcome of trials investigating proactive sequencing of endocrine therapies, we present a model based on several trials, including ATAC. This model suggests that using an aromatase inhibitor as initial adjuvant therapy is a better option than switching to an aromatase inhibitor after >/=2 years of tamoxifen. The relative toxicities of the three approved third-generation aromatase inhibitors, anastrozole, letrozole, and exemestane, are discussed. These data suggest that long-term safety profiles may differ between aromatase inhibitors, although comprehensive comparative data for letrozole and exemestane versus tamoxifen are lacking.
Adjuvant aromatase inhibitor therapy for early breast cancer: A review of the most recent data. [2018]Tamoxifen is the established adjuvant treatment for postmenopausal women with hormone-sensitive early breast cancer. However, the side-effects associated with tamoxifen therapy have prompted a search for safer and potentially more effective endocrine agents. Results from randomized trials of the third-generation aromatase inhibitors, anastrozole, letrozole and exemestane, demonstrating improved efficacy compared with tamoxifen and favorable tolerability profiles, are discussed in this review.
Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. [2022]The Arimidex (anastrozole), Tamoxifen, Alone or in Combination (ATAC) trial was designed to compare the efficacy and safety of anastrozole with tamoxifen as adjuvant treatment for postmenopausal women with early-stage breast cancer. After an extended follow-up beyond the 5 years of treatment, we aimed to assess the safety, tolerability, and risk-benefit indices of these compounds.
The FACE trial: letrozole or anastrozole as initial adjuvant therapy? [2018]The adjuvant Femara versus Anastrozole Clinical Evaluation (FACE) trial compares upfront therapy letrozole 2.5 mg with anastrozole 1 mg daily for up to 5 years in postmenopausal, hormone receptor-positive, node-positive breast cancer patients. This phase III b open label, randomized, multicenter study will include 4000. patients from up to 250 international sites. Patients will be stratified by degree of lymph node involvement and HER-2 status. Any efficacy and safety difference of the two drugs will be reported. Primary objective is DFS, secondary objectives are safety, OS, time to distant metastases, time to contralateral breast cancer and breast cancer specific survival.
Choosing early adjuvant therapy for postmenopausal women with hormone-sensitive breast cancer: aromatase inhibitors versus tamoxifen. [2018]The aromatase inhibitors (AIs) anastrozole, exemestane, and letrozole have demonstrated superior disease-free survival (DFS) over tamoxifen in several trials. As the choice of adjuvant endocrine treatment for early breast cancer (EBC) is evolving from tamoxifen to the AIs, this review compares the AIs with tamoxifen to help surgeons choose a treatment plan that provides the greatest reduction of recurrence risk for their patients.
Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. [2022]The aromatase inhibitor letrozole, as compared with tamoxifen, improves disease-free survival among postmenopausal women with receptor-positive early breast cancer. It is unknown whether sequential treatment with tamoxifen and letrozole is superior to letrozole therapy alone.