A Phase III Adjuvant Trial Evaluating the Addition of Adjuvant Chemotherapy to Ovarian Function Suppression Plus Endocrine Therapy in Premenopausal Patients With pN0-1, ER-Positive/HER2-Negative Breast Cancer and an Oncotype Recurrence Score Less Than or Equal to 25 (OFSET)

Plain English Summary

Evaluating the Addition of Adjuvant Chemotherapy to Ovarian Function Suppression Plus Endocrine Therapy in Premenopausal Patients With pN0-1, ER-Positive/HER2-Negative Breast Cancer and an Oncotype Recurrence Score Less Than or Equal to 25 is a Phase 3 clinical trial sponsored by NRG Oncology studying Breast Cancer. This trial tests if adding chemotherapy to standard hormone therapy (ovarian suppression + endocrine therapy) improves outcomes for premenopausal women with early-stage, ER-positive, HER2-negative breast cancer. It is for women who are premenopausal (have not gone through menopause) and have early-stage breast cancer that is ER-positive and HER2-negative, with a specific genetic marker (Oncotype Recurrence Score) indicating a moderate risk of recurrence. Participation involves being randomly assigned to receive either the standard hormone therapy alone or the standard hormone therapy plus chemotherapy. This includes regular clinic visits, tests, and potential side effects from treatment. Alternatives include standard hormone therapy alone, or in some cases, other treatment combinations based on individual risk assessment and doctor's recommendation. The trial aims to enroll 3960 participants.

Official Summary

This Phase III Trial will determine whether adjuvant chemotherapy (ACT) added to ovarian function suppression (OFS) plus endocrine therapy (ET) is superior to OFS plus ET in improving invasive breast cancer-free survival (IBCFS) among premenopausal, early- stage breast cancer (EBC) patients with estrogen receptor (ER)-positive, HER2-negative tumors and 21-gene recurrence score (RS) between 16-25 (for pN0 patients) and 0-25 (for pN1 patients).

Who Can Participate

Here is what you need to know about eligibility for this trial. Women who are premenopausal (defined by age and menstrual cycle, or hormone levels if periods have stopped) and are 18 years or older can join. Patients must have early-stage breast cancer (ER-positive, HER2-negative) with specific lymph node involvement (pN0-1) and a certain Oncotype Recurrence Score (16-25 for node-negative, or less than 26 for 1-3 nodes positive). Patients with certain prior breast cancer treatments or surgeries may be eligible if margins are clear or will be treated with radiation. Patients with other active cancers may not be eligible. Individuals with a MammaPrint 'High Risk' result are not eligible for this study. This trial is studying Breast Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome, invasive breast cancer-free survival, measures how long patients live without their breast cancer returning in an invasive form, indicating the effectiveness of the treatment in p The specific primary outcome measures are: Invasive breast cancer-free survival (IBCFS) (Time from randomization for duration of trial, 11 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a gap in understanding whether adding chemotherapy to standard hormone therapy can further reduce the risk of breast cancer returning in premenopausal women with specific tumor ch As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Breast Cancer, where improved treatment options are needed.

Investor Insight

This Phase III trial, sponsored by NRG Oncology, is a large-scale study (3960 participants) aiming to refine treatment for a significant subset of early-stage breast cancer patients, potentially impac Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 3960 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor about the specific chemotherapy drugs that might be used, the duration of treatment, and how this trial's approach compares to standard care for your specific situation. Participation will involve regular clinic visits for monitoring, receiving treatments (hormone therapy and potentially chemotherapy), and undergoing various tests and scans. Be prepared for potential side effects from both hormone therapy and chemotherapy, and discuss any concerns about managing these with your healthcare team. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 3,960 participants

Interventions

• DRUG: Ovarian Function Suppression + Aromatase Inhibitor — Aromatase inhibitor co-administered with a 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
• DRUG: Adjuvant Chemotherapy + Ovarian Function Suppression — 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 investiga

Primary Outcomes

• Invasive breast cancer-free survival (IBCFS) (Time from randomization for duration of trial, 11 years)

Secondary Outcomes

• Invasive disease-free survival (IDFS) (Time from randomization for duration of trial, 11 years)
• Overall survival (Time from randomization for duration of trial, 11 years)
• Distant recurrence-free interval (DRFI) (Time from randomization for duration of trial, 11 years)
• Breast cancer-free interval (BCFI) (Time from randomization for duration of trial, 11 years)
• Menopausal symptoms measured by the FACT ESS-19 score (Measured at one year after randomization)

Full Eligibility Criteria

Inclusion Criteria:

* A patient cannot be considered eligible for this study unless ALL of the following conditions are met.

  * The patient or a legally authorized representative must provide study-specific informed consent prior to pre-entry and, for patients treated in the U.S., authorization permitting release of personal health information.
  * Female patients must be greater than or equal to 18 years of age.
  * Patients must be premenopausal (evidence of functioning ovaries) at the time of pre-entry. For study purposes, premenopausal is defined as:
  * Age 50 years or under with spontaneous menses within 12 months; or
  * Age greater than 50-60 years with spontaneous menses within 12 months plus follicle-stimulating hormone (FSH) and estradiol levels in the premenopausal range; or
  * Patients with amenorrhea due to IUD or prior uterine ablation must have FSH and estradiol levels in the premenopausal range; or
  * Patients with prior hysterectomy must have FSH and estradiol levels in the premenopausal range.
  * The patient must have an ECOG performance status of less than or equal to 2 (or Karnofsky greater than or equal to 60%).
  * Patients may have ipsilateral or contralateral synchronous breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
  * Patients may have multicentric or multifocal breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
  * Patient may have undergone a total mastectomy, skin-sparing mastectomy, nipple-sparing mastectomy, or a lumpectomy.
  * For patients who undergo a lumpectomy, the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS (ductal carcinoma in situ) with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. Positive posterior margin is allowed if surgeon deems no further resection possible. (Patients with margins positive for LCIS (lobular carcinoma in situ) are eligible without additional resection.)
  * For patients who undergo mastectomy, the margins must be free of residual gross tumor. (Patients with microscopic positive margins are eligible if post-mastectomy RT (radiation therapy) of the chest wall will be administered.)
  * Patient must have undergone axillary staging with sentinel node biopsy (SNB), targeted axillary dissection (TAD), or axillary lymph node dissection (ALND).
  * The following staging criteria must be met postoperatively according to AJCC 8th edition criteria:
  * By pathologic evaluation, primary tumor must be pT1-3. (If N0, must be T1c or higher.)
  * By pathologic evaluation, ipsilateral nodes must be pN0 or pN1 (pN1mi, pN1a, pN1b, pN1c).
  * Patients with positive isolated tumor cells (ITCs) in axillary nodes will be considered N0 for eligibility purposes.
  * Patients with micrometastatic nodal involvement (0.2-2 mm) will be considered N1.
  * Oncotype DX RS (recurrence score) requirements\*:
  * If node-negative:
  * Oncotype DX RS must be RS 21-25, or
  * Oncotype DX RS must be 16-20 and disease must be high clinical risk, defined as: low histologic grade with primary tumor size greater than 3 cm, intermediate histologic grade with primary tumor size greater than 2 cm, or high histologic grade with primary tumor size greater than 1 cm.
  * If 1-3 nodes involved:
  * Oncotype DX RS must be less than 26.

    \* Patients with a "Low Risk" or "MP1" MammaPrint (a genomic test that analyzes the activity of certain genes in early-stage breast cancer) result must have eligibility assessed with an Oncotype DX RS at pre-entry (see Section 3.1). Blocks or unstained slides must be sent to the Genomic Health centralized laboratory for testing at no cost to these patients. If MammaPrint High Risk or MP2, these patients are not eligible.
  * The tumor must be ER and/or PgR-positive (progesterone receptor) by current ASCO/CAP guidelines based on local testing results. Patients with greater than or equal to 1% ER and/or PgR staining by IHC will be classified as positive.
  * The tumor must be HER2-negative by current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines based on local testing results.
  * The interval between the last surgery for breast cancer (including re-excision of margins) and pre-entry must be no more than 16 weeks.
  * Short course of endocrine therapy of less than 6 weeks duration before pre-entry is acceptable either as neoadjuvant or adjuvant therapy. An Oncotype DX RS must be performed on core biopsy specimen obtained prior to initiation of neoadjuvant endocrine therapy if received.
  * Patients with a prior or concurrent non-breast malignancy whose natural history or treatment does not have the potentia

Trial Locations

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• Anchorage Associates in Radiation Medicine, Anchorage, Alaska, United States
• Anchorage Radiation Therapy Center, Anchorage, Alaska, United States
• Alaska Breast Care and Surgery LLC, Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC, Anchorage, Alaska, United States
• Alaska Women's Cancer Care, Anchorage, Alaska, United States
• Anchorage Oncology Centre, Anchorage, Alaska, United States
• Katmai Oncology Group, Anchorage, Alaska, United States
• Providence Alaska Medical Center, Anchorage, Alaska, United States
• Kingman Regional Medical Center, Kingman, Arizona, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• ER-Positive Breast Cancer
• HER2-Negative Breast Cancer
• Premenopausal Breast Cancer
• Early-Stage Breast Cancer
• Hormone Receptor-Positive Breast Cancer
• Node-Positive Breast Cancer
• Node-Negative Breast Cancer
• Adjuvant Therapy
• Endocrine Therapy

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