A Phase III Trial of Rx Therapy Guided by Genomic Risk Assessment For High Anatomic Stage ER-pos/HER2-neg Breast Cancer With RS</=25 (RxFINE-Low)

Plain English Summary

Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Estrogen Receptor-Positive Breast Carcinoma, HER2-Negative Breast Carcinoma. This trial tests if hormone therapy combined with a drug called ribociclib is as effective as chemotherapy followed by hormone therapy and ribociclib. It is for women and men with early-stage breast cancer that is estrogen receptor-positive (ER+) and HER2-negative, with a low risk of the cancer returning. Participation involves being randomly assigned to one of two treatment groups and undergoing regular medical check-ups and tests. Standard treatment for this type of breast cancer is the alternative, which may involve chemotherapy, hormone therapy, or both. The trial aims to enroll 1978 participants.

Official Summary

This phase III trial compares standard of care hormone therapy plus ribociclib to chemotherapy followed by hormone therapy plus ribociclib for the treatment of patients with high anatomic stage breast cancer with low risk of the cancer returning (low risk recurrence). Ribociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hormone therapy, with letrozole, anastrozole or exemestane, lowers the amount of estrogen made by the body. This may help stop the growth of tumor cells that need estrogen to grow. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Hormone therapy plus ribociclib may work as well as chemotherapy followed by hormone therapy plus ribociclib for the treatment of high anatomic stage breast cancer with low recurrence risk.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are 18 or older, have ER+/HER2- breast cancer that has not spread, and have a low risk of recurrence based on a test called Oncotype DX. You cannot join if you have a history of other cancers that could interfere with treatment, or if your breast cancer is HER2-positive or ER-negative. Men and postmenopausal women are eligible; specific criteria define postmenopausal status. Your cancer must be staged according to specific criteria (AJCC 8th edition), and surgical margins must be clear or managed with radiation. This trial is studying Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Estrogen Receptor-Positive Breast Carcinoma, HER2-Negative Breast Carcinoma, so participants generally need a confirmed diagnosis.

What They're Measuring

The main goal is to see if patients remain free of invasive breast cancer or death for up to 10 years, meaning it measures how well the treatments prevent the cancer from coming back or spreading. The specific primary outcome measures are: Invasive breast cancer-free survival (iBCFS) (From randomization to invasive disease or death, up to 10 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 aims to find a less intensive treatment for early-stage ER+/HER2- breast cancer with a low risk of recurrence, potentially avoiding the side effects of chemotherapy. 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 Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Estrogen Receptor-Positive Breast Carcinoma, HER2-Negative Breast Carcinoma, where improved treatment options are needed.

Investor Insight

This trial addresses a significant market for early-stage breast cancer treatments, seeking to optimize therapy for a specific patient subgroup and potentially establish a new standard of care. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 1978 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor about the specific treatments you might receive in each group and the potential side effects. Understand how your participation will be decided randomly and what tests and appointments will be required. Be prepared for regular blood draws, scans, and clinic visits throughout the trial. The trial is being conducted at multiple 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: 1,978 participants

Interventions

• DRUG: Anastrozole — Given PO
• PROCEDURE: Biospecimen Collection — Undergo blood sample collection
• PROCEDURE: Bone Scan — Undergo bone scan
• DRUG: Chemotherapy — Receive standard of care chemotherapy
• PROCEDURE: Computed Tomography — Undergo CT scan

Primary Outcomes

• Invasive breast cancer-free survival (iBCFS) (From randomization to invasive disease or death, up to 10 years)

Secondary Outcomes

• Invasive disease free survival (From randomization to the first occurrence of invasive disease or death, up to 10 years)
• Distant disease free survival (Up to 10 years)
• Distant recurrence free survival (Up to 10 years)
• Recurrence-free interval (Up to 10 years)
• Overall survival (From randomization to death, up to 10 years)

Full Eligibility Criteria

Inclusion Criteria:

* STEP 0: Patient must be ≥ 18 years of age
* STEP 0: Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 28 days prior to Step 0 pre-registration
* STEP 0: Patient must be a postmenopausal woman or a man

  * NOTE: Menopause can be determined by any of the following:

    * Prior bilateral oophorectomy
    * Age ≥ 60 years
    * Age \< 60 years with amenorrhea for ≥ 12 months and estradiol and follicle stimulating hormone (FSH) levels in the postmenopausal range
  * NOTE: FSH and estradiol levels should be repeated as clinically indicated to ensure menopausal status in patients with breast cancer with chemotherapy-induced amenorrhea
* STEP 0: Patient must meet one of the following staging criteria postoperatively according to American Joint Committee on Cancer (AJCC) 8th edition criteria

  * pT0-T3 with 3 positive ipsilateral lymph nodes (micro-or macrometastatic disease) and no planned axillary lymph node dissection after definitive surgery in the breast and axilla with curative intent.
  * pT0-T3 with N2 or N3
  * pT3 with N0-N3

    * NOTES:

      * Patients with T4 breast cancer are not eligible.
      * Positive isolated tumor cells (ITCs) in axillary nodes without micro- or macrometastasis are considered N0 for eligibility purposes.
      * ITC does not contribute to nodal count for staging purposes
* STEP 0: Patient must have a primary breast tumor that is estrogen receptor (ER) positive with \> 10% ER expression by immunohistochemistry (IHC) as per 2020 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Estrogen Receptor Testing Guideline.

  * NOTE: ER 1-10% are reported as ER low positive. These tumors have less endocrine-sensitive disease and are not eligible)
* STEP 0: Patient must have a primary breast tumor that is HER2-negative by current ASCO/CAP guidelines utilizing immunohistochemistry and/or fluorescence in situ hybridization (FISH)
* STEP 0: Patient may have multicentric or multifocal breast cancer if the highest stage tumor meets eligibility criteria outlined above, and the tumor sites are felt to represent a single disease process by local pathology or other sites of disease are also ER-positive (\> 10%) and HER2 negative, if such testing is completed. If local pathology feels that multicentric or multifocal disease may represent distinct disease processes repeat disease receptor testing is required other sites of disease must also be also ER-positive (\> 10%) and HER2-negative
* STEP 0: For patients who have undergone a lumpectomy, the margins of the resected specimen or re-excision must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) 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 lobular carcinoma in situ (LCIS) are eligible without additional resection
* STEP 0: For patients who have undergone mastectomy, the margins must be free of residual gross tumor. Patients with microscopic positive margins are eligible if post-mastectomy radiation treatment (RT) of the chest wall will be administered
* STEP 0: Patient must have undergone axillary staging with sentinel lymph node biopsy (SLNB), targeted axillary dissection (TAD), or axillary lymph node dissection (ALND)
* STEP 0: Patient must have no evidence of locoregional or distant metastatic disease by clinical history and physical exam. Treating physician can consider additional imaging evaluation per National Comprehensive Cancer Network (NCCN) guidelines and/or institutional practice
* STEP 0: Patient must be able to have Oncotype DX testing performed.

  * If Oncotype DX testing was previously performed, the results of Recurrence Score (RS) must be available and must meet Step 1 eligibility criteria.
  * If Oncotype DX testing was not performed yet, tissue from the core, excisional biopsy or surgical specimen of the tumor lesion must be available and must be shipped to Exact Sciences for determination of the Oncotype DX Recurrence Score (RS) for eligibility and stratification.

    * NOTE: Exact Sciences will notify the submitting institution of Recurrence Score results within two (2) weeks of receipt of the tumor specimen. Institutions will receive an email notification of eligibility status once Recurrence Score results are entered into Rave by the submitting institution
* STEP 0: Patient must have had their final cancer surgery for breast cancer (including re-excision of margins) less than 16 weeks prior to Step 0 Pre-Registration.

  * NOTE: This excludes additional surgery for reconstructive purposes
* STEP 0: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy a

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Estrogen Receptor-Positive Breast Cancer
• HER2-Negative Breast Cancer
• Anatomic Stage II Breast Cancer
• Anatomic Stage IIIA Breast Cancer
• Anatomic Stage IIIC Breast Cancer
• Metastatic Breast Cancer (for context of advanced disease)
• Oncologic Therapies
• Hormone Therapy
• Chemotherapy

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