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

NCT07391774 | Not Yet Recruiting Phase 3 FDA Drug

• 3 other identifiers: NCI-2026-00634EA1242U10CA180820
• Study Type: interventional
• Target: 1,978
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Anatomic Stage IIIC Breast Cancer AJCC v8; Estrogen Receptor-Positive Breast Carcinoma; HER2-Negative Breast Carcinoma; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Invasive breast cancer-free survival (iBCFS)

  Invasive disease defined as the first occurrence of one of the following events: local invasive recurrence following mastectomy, local invasive recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, or contralateral invasive breast cancer. The distribution of iBCFS will be estimated using the Kaplan-Meier method. The hazard ratio will be estimated using Cox proportional hazard model. The primary analysis will compare treatment groups defined by the randomized treatment assignment (intent-to-treat analysis). A secondary analysis will be performed comparing groups defined by treatment received (per protocol analysis).

  From randomization to invasive disease or death, up to 10 years

Secondary Outcomes (8)

• 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

Other Outcomes (3)

• Primary outcome treatment effect by sex

  Up to 10 years

• Primary outcome treatment effect by race

  Up to 10 years

• Primary outcome treatment effect by ethnicity

  Up to 10 years

Study Arms (2)

Arm A (chemotherapy, hormone therapy, ribociclib)

EXPERIMENTAL

Patients receive their physician's choice of standard of care chemotherapy. Patients then receive their physician's choice of standard of care hormone therapy with letrozole, anastrozole, or exemestane PO QD on days 1-28 of each cycle, as well as ribociclib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days for at least 60 months for hormone therapy and up to 3 years for ribociclib, in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan, bone scan, or FDG PET-CT scan and may optionally undergo blood sample collection throughout the study.

Drug: Anastrozole; Procedure: Biospecimen Collection; Procedure: Bone Scan; Drug: Chemotherapy; Procedure: Computed Tomography; Drug: Exemestane; Drug: Letrozole; Procedure: Oncotype DX Breast Cancer Assay; Procedure: Positron Emission Tomography

Arm B (hormone therapy, ribociclib)

EXPERIMENTAL

Patients receive their physician's choice of standard of care hormone therapy with letrozole, anastrozole, or exemestane PO QD on days 1-28 of each cycle and ribociclib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days for at least 60 months for hormone therapy and up to 3 years for ribociclib, in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, bone scan, or FDG PET-CT scan and may optionally undergo blood sample collection throughout the study.

Drug: Anastrozole; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Exemestane; Drug: Letrozole; Procedure: Oncotype DX Breast Cancer Assay; Procedure: Positron Emission Tomography; Drug: Ribociclib Succinate

Interventions

Chemotherapy DRUG

Receive standard of care chemotherapy

Also known as: Chemo, Chemotherapy (NOS), Chemotherapy, Cancer, General

Arm A (chemotherapy, hormone therapy, ribociclib)

Exemestane DRUG

Given PO

Also known as: Aromasin, FCE-24304

Arm A (chemotherapy, hormone therapy, ribociclib); Arm B (hormone therapy, ribociclib)

Letrozole DRUG

Given PO

Also known as: CGS 20267, CGS-20267, CGS20267, Femara, Fempro

Arm A (chemotherapy, hormone therapy, ribociclib); Arm B (hormone therapy, ribociclib)

Oncotype DX Breast Cancer Assay PROCEDURE

Undergo risk recurrence testing

Also known as: Oncotype DX

Arm A (chemotherapy, hormone therapy, ribociclib); Arm B (hormone therapy, ribociclib)

Positron Emission Tomography PROCEDURE

Undergo FDG PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Arm A (chemotherapy, hormone therapy, ribociclib); Arm B (hormone therapy, ribociclib)

Anastrozole DRUG

Given PO

Also known as: Anastrazole, Arimidex, ICI D1033, ICI-D1033, ZD-1033

Arm A (chemotherapy, hormone therapy, ribociclib); Arm B (hormone therapy, ribociclib)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm A (chemotherapy, hormone therapy, ribociclib); Arm B (hormone therapy, ribociclib)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Arm A (chemotherapy, hormone therapy, ribociclib); Arm B (hormone therapy, ribociclib)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm A (chemotherapy, hormone therapy, ribociclib); Arm B (hormone therapy, ribociclib)

Ribociclib Succinate DRUG

Given PO

Also known as: Kisqali

Arm B (hormone therapy, ribociclib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Interventions

Anastrozole; Specimen Handling; Drug Therapy; exemestane; Letrozole; Magnetic Resonance Spectroscopy; ribociclib

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Therapeutics; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Nancy Chan

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2026
• First Posted: February 6, 2026
• Study Start (Estimated): July 7, 2026
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): July 31, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share