Chemotherapy + Hormone Therapy for Breast Cancer

(OFSET Trial)

Recruiting in Palo Alto (17 mi)

+1126 other locations

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: NRG Oncology

Must be taking: Endocrine therapy

Must not be taking: Hormonally based contraceptives

Disqualifiers: Metastatic disease, Cardiac disease, others

Stay on Your Current Meds

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing if adding additional cancer-fighting drugs to treatments that stop certain body functions is better than just using the treatments that stop those functions alone. It targets younger women with early-stage breast cancer who have a higher risk of dying from the disease. The treatment works by stopping certain body functions and using drugs to kill cancer cells.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does require that hormonally based contraceptives be discontinued before joining. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Adjuvant Chemotherapy + Ovarian Function Suppression for breast cancer?

Research shows that ovarian function suppression (OFS) with tamoxifen or aromatase inhibitors (AIs) can improve disease-free survival in premenopausal women with breast cancer, especially those at higher risk of recurrence.

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Is the combination of chemotherapy and hormone therapy generally safe for humans?

The research indicates that aromatase inhibitors (a type of hormone therapy) can lead to ovarian function recovery in women who experienced ovarian failure due to chemotherapy. This recovery can affect hormone levels, but the studies do not report severe safety concerns related to the combination of chemotherapy and hormone therapy.

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How is the treatment Ovarian Function Suppression + Aromatase Inhibitor unique for breast cancer?

This treatment is unique because it combines ovarian function suppression (which stops the ovaries from producing hormones) with aromatase inhibitors (which block estrogen production) to improve disease-free survival in premenopausal women with breast cancer, especially those at higher risk of recurrence.

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Eligibility Criteria

This trial is for premenopausal women at least 18 years old with early-stage, ER-positive/HER2-negative breast cancer and a low to intermediate recurrence score. They must have had surgery for breast cancer within the last 16 weeks and be eligible for radiation therapy. Women can't join if they are pregnant, breastfeeding, have severe heart issues, other non-breast cancers that could affect the study's safety or results, or any metastatic disease.

Inclusion Criteria

I have another cancer type, but it won't affect this cancer treatment's safety or results.

I have breast cancer in more than one location, but only the largest tumor needs treatment according to the trial's criteria.

I have breast cancer in one or both breasts, but only the highest stage tumor qualifies for this trial and the other tumors don't need chemotherapy or HER2 therapy.

Exclusion Criteria

Your recent lab test results show any of the following values.

I have a heart condition or have been treated with heart-toxic drugs and need a heart function assessment.

My breast cancer is not the common type; it's a rare form like sarcoma or lymphoma.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adjuvant chemotherapy followed by ovarian function suppression and endocrine therapy

5 years

Monthly or every-three-months visits for GnRH agonist administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

11 years

Participant Groups

The trial is testing if adding adjuvant chemotherapy to ovarian function suppression plus endocrine therapy improves survival without invasive breast cancer returning in patients with certain types of early-stage breast cancer compared to just ovarian function suppression plus endocrine therapy.

Group I: Arm 2 Adjuvant Chemotherapy + Ovarian Function Suppression + Aromatase Inhibitor Active Control 2 Interventions

Adjuvant chemotherapy of investigator's choice followed by an aromatase inhibitor (AI) co-administered with an GnRH agonist for 5 years. The choice of AI is per investigator discretion. The choice of GnRH agonist and dosing schedule is per investigator's discretion. Options commonly include goserelin, leuprolide, or triptorelin given monthly or every-three-months. The dose and schedule of AI should be consistent with the drug package insert. Endocrine treatment beyond 5 years is at the investigator's discretion. Bilateral oophorectomy may substitute for ovarian suppression if desired.

Group II: Arm 1: Ovarian Function Suppression + Aromatase Inhibitor Active Control 1 Intervention

Aromatase inhibitor co-administered with a GnRH agonist (gonadotropin releasing hormone) for 5 years. The choice of AI is per investigator discretion. The choice of GnRH agonist and dosing schedule is per investigator's discretion. Options commonly include goserelin, leuprolide, or triptorelin given monthly or every-three-months. The dose and schedule of AI should be consistent with the drug package insert. Endocrine treatment beyond 5 years is at the investigator's discretion. Bilateral oophorectomy may substitute for ovarian suppression if desired.

Ovarian Function Suppression + Aromatase Inhibitor is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Ovarian Function Suppression + Aromatase Inhibitor for:

• Hormone receptor-positive, HER2-negative breast cancer in premenopausal women

🇪🇺 Approved in European Union as Ovarian Function Suppression + Aromatase Inhibitor for:

• Early-stage hormone receptor-positive, HER2-negative breast cancer in premenopausal women

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Hennepin County Medical Center Minneapolis, MN

Wayne Hospital Greenville, OH

ThedaCare Cancer Care - Waupaca Waupaca, WI

MD Anderson West Houston Houston, TX

More Trial Locations

Who Is Running the Clinical Trial?

NRG Oncology Lead Sponsor

National Cancer Institute (NCI) Collaborator

References

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

Effectiveness of Adjuvant Ovarian Function Suppression in Premenopausal Women With Early Breast Cancer: A Multicenter Cohort Study. [2021] Ovarian function suppression (OFS) with tamoxifen or aromatase inhibitors (AIs) improves disease-free survival in premenopausal women with breast cancer, mostly in those at higher risk of recurrence. However, its real-world use and impact remain poorly understood.

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

Ovarian Function Recovery During Anastrozole in Breast Cancer Patients With Chemotherapy-Induced Ovarian Function Failure. [2022] Aromatase inhibitors (AIs) are given as adjuvant therapy for hormone receptor-positive breast cancer in postmenopausal women, also to those with chemotherapy-induced ovarian function failure. The current analysis reports on endocrine data of patients with chemotherapy-induced ovarian function failure who were included in the phase III DATA study assessing different durations of adjuvant anastrozole after tamoxifen.

3. England pubmed.ncbi.nlm.nih.gov

Predictors of recovery of ovarian function during aromatase inhibitor therapy. [2022] Aromatase inhibitors (AIs) may cause a rise in estrogen levels due to ovarian function recovery in women with clinical chemotherapy-induced ovarian failure (CIOF). We carried out a prospective registry trial to identify predictors of ovarian function recovery during AI therapy.

4. England pubmed.ncbi.nlm.nih.gov

Incidence and predictors of ovarian function recovery (OFR) in breast cancer (BC) patients with chemotherapy-induced amenorrhea (CIA) who switched from tamoxifen to exemestane. [2022] Aromatase inhibitors (AIs) may promote ovarian function recovery (OFR). True incidence, predictors and impact on the outcome of OFR are unknown.

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

Incidence and Predictive Factors for Recovery of Ovarian Function in Amenorrheic Women in Their 40s Treated With Letrozole. [2018] This prospective study assessed the impact of 2 years of aromatase inhibitor (AI) therapy on the incidence of ovarian function recovery (OFR) in women age 40 to 49 with estrogen receptor-positive breast cancer who were premenopausal at diagnosis and who underwent chemotherapy-induced amenorrhea during adjuvant treatment.

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

Measurable Serum Estradiol and Estrone in Women 36-56 Years During Adjuvant Treatment With Aromatase Inhibitors for a Hormone Receptor-Positive Breast Cancer. Case Studies and Cross-sectional Study Using an Ultra-sensitive LC-MS/MS-Method. [2023] Ovarian function recovery (OFR) during adjuvant use of an aromatase inhibitor (AI) negatively impacts breast cancer outcome. We measured serum FSH and estrogen levels in consecutive AI-users with an uncertain menopausal status during follow-up and report associated risk factors of OFR METHODS: A retrospective cross sectional observational monocentric study including breast cancer patients in follow-up using an adjuvant AI, age 36 to 56 years, with at least one serum estradiol (E2) and estrone (E1) measurement between 2013 and 2020. Estrogens were quantified using a sensitive liquid chromatography-tandem mass spectrometry method (LC-MS/MS). Women on LHRH agonist were included while those with a bilateral oophorectomy or ovarian irradiation were not. We aimed to identify risk factors of OFR considering age, body mass index (BMI), previous chemotherapy and duration of AI use. Univariable analysis was used to evaluate risk factors of OFR.

7. England pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors: are there differences between steroidal and nonsteroidal aromatase inhibitors and do they matter? [2008] Aromatase inhibitors (AIs) are approved for use in both early- and advanced-stage breast cancer in postmenopausal women. Although the currently approved "third-generation" AIs all powerfully inhibit estrogen synthesis, they may be subdivided into steroidal and nonsteroidal inhibitors, which interact with the aromatase enzyme differently. Nonsteroidal AIs bind noncovalently and reversibly to the aromatase protein, whereas steroidal AIs may bind covalently and irreversibly to the aromatase enzyme. The steroidal AI exemestane may exert androgenic effects, but the clinical relevance of this has yet to be determined. Switching between steroidal and nonsteroidal AIs produces modest additional clinical benefits, suggesting partial noncrossresistance between the classes of inhibitor. In these circumstances, the response rates to the second AI have generally been low; additional research is needed regarding the optimal sequence of AIs. To date, clinical studies suggest that combining an estrogen-receptor blocker with a nonsteroidal AI does not improve efficacy, while combination with a steroidal AI has not been evaluated. Results from head-to-head trials comparing steroidal and nonsteroidal AIs will determine whether meaningful clinical differences in efficacy or adverse events exist between the classes of AI. This review summarizes the available evidence regarding known differences and evaluates their potential clinical impact.

8. England pubmed.ncbi.nlm.nih.gov

Aromatase, its inhibitors and their use in breast cancer treatment. [2019] Aromatase, a cytochrome P450 enzyme, catalyses the rate-limiting step in the biosynthesis of estrogens. Many processes in male and female development and reproduction and especially in the growth of hormone-dependent cancers, are dependent on estrogens. Therefore, controlling estrogen production by inhibition of aromatase is a logical treatment strategy. Two classes of aromatase inhibitors, steroidal and non-steroidal compounds, are now coming into use. Among the steroid substrate analogs, 4-hydroxyandrostenedione has been shown to be effective in breast cancer patients with advanced disease and was recently approved for treatment in the United Kingdom. Several highly potent and selective non-steroidal inhibitors are now in clinical trials. The variety of compounds that act as aromatase inhibitors should provide breast cancer patients with a number of new treatment options.