Impact of Omitting Chemo Based on Patient's Selection for ER-Positive, HER2-Negative Breast Cancer With Ribociclib and Endocrine Therapy

NCT06953882 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2000038734BCRF-23-184
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II Trial to assess the impact of omitting adjuvant chemotherapy based on patient's selection on treatment persistence of CDK4/6 inhibitor, ribociclib (Kisqali), in a well-defined subgroup of patients with resected estrogen receptor (ER)-positive, HER2-negative, lymph node-positive breast cancer, but whose tumor profiling indicates a less aggressive biological nature (OncotypeDx 21-gene recurrence score RS 0-25).

Conditions

HER2 Negative Breast Cancer

Keywords

premenopausal women T1-3N1-2; postmenopausal women T3N1; postmenopausal women T3N2; ER-positive

Outcome Measures

Primary Outcomes (1)

• Discontinuation rate of ribociclib in patients with resected moderate to high-anatomical risk, low-genomic risk, ER-positive, HER2-negative breast cancer

  Discontinuation rate of ribociclib in participants with resected moderate to high-anatomical risk (men or premenopausal women T1-3N1-2, and postmenopausal women T3N1 or T1-3N2), low-genomic risk (RS≤ 25), ER-positive, HER2-negative breast cancer who choose to forgo or include adjuvant chemotherapy in their treatment regimen. One-year treatment discontinuation is defined as treatment discontinuation within one year for any reason (e.g., adverse events, disease recurrence, patient/investigator decision, lost to follow up, etc).

  Within one year of treatment

Secondary Outcomes (8)

• Invasive disease-free survival in patients with resected moderate to high-anatomical risk, low-genomic risk, ER-positive, HER2-negative breast cancer

  Defined as the time from initiation of treatment to three years post-survival

• Change from Baseline in Severity of Symptoms in patients with resected moderate to high-anatomical risk, low-genomic risk, ER-positive, HER2-negative breast cancer

  At baseline, every three months during the first year and every six months during years 2 and 3

• Change from Baseline in Physical Functioning and Global Health Status/Quality of Life in patients with resected moderate to high-anatomical risk, low-genomic risk, ER-positive, HER2-negative breast cancer

  At baseline, every three months during the first year and every six months during years 2 and 3

• Factors Impacting Decision Making in Adjuvant Treatment Decisions in patients with resected moderate to high-anatomical risk, low-genomic risk, ER-positive, HER2-negative breast cancer

  At baseline

• Changes in fear of cancer recurrence in patients with resected moderate to high-anatomical risk, low-genomic risk, ER-positive, HER2-negative breast cancer

  At baseline, six months, and one year

Study Arms (2)

Ribociclib + Optimized Endocrine Therapy

EXPERIMENTAL

Combination of ribociclib and optimized endocrine therapy

Drug: Ribociclib 400mg; Drug: Letrozole 2.5mg; Drug: Anastrazole 1mg; Drug: Goserelin 3.6 MG

Adjuvant Chemotherapy + Ribociclib & Optimized Endocrine Therapy

EXPERIMENTAL

Adjuvant chemotherapy followed by a combination of ribociclib and optimized endocrine therapy

Drug: Ribociclib 400mg; Drug: Letrozole 2.5mg; Drug: Anastrazole 1mg; Drug: Goserelin 3.6 MG; Radiation: Adjuvant chemotherapy

Interventions

Ribociclib 400mg DRUG

400 mg (2 x 200 mg tablets by mouth) once daily on days 1 to 21 of a 28-day cycle, followed by seven days off ribociclib (Days 22 to 28).

Adjuvant Chemotherapy + Ribociclib & Optimized Endocrine Therapy; Ribociclib + Optimized Endocrine Therapy

Letrozole 2.5mg DRUG

Letrozole will be administered as an endocrine therapy. The regimen will differ depending on the demographic of the patient. For postmenopausal women: Letrozole 2.5 mg by mouth daily continuously. For men or premenopausal women: Letrozole 2.5 mg by mouth daily continuously.

Adjuvant Chemotherapy + Ribociclib & Optimized Endocrine Therapy; Ribociclib + Optimized Endocrine Therapy

Anastrazole 1mg DRUG

For postmenopausal women: Letrozole 2.5 mg by mouth daily continuously or anastrozole 1 mg by mouth daily continuously. For men or premenopausal women: Letrozole 2.5 mg by mouth daily continuously or anastrozole 1 mg by mouth daily continuously.

Adjuvant Chemotherapy + Ribociclib & Optimized Endocrine Therapy; Ribociclib + Optimized Endocrine Therapy

Goserelin 3.6 MG DRUG

For men or premenopausal women: Letrozole 2.5 mg by mouth daily continuously or anastrozole 1 mg by mouth daily continuously, concurrently with goserelin 3.6 mg monthly injection.

Adjuvant Chemotherapy + Ribociclib & Optimized Endocrine Therapy; Ribociclib + Optimized Endocrine Therapy

Adjuvant chemotherapy RADIATION

Adjuvant chemotherapy dose modifications in Arm 2 will be per institutional guidelines and investigator discretion.

Adjuvant Chemotherapy + Ribociclib & Optimized Endocrine Therapy

Eligibility Criteria

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

You may qualify if:

• Female or male age ≥ 18 years old and have the ability to understand and the willingness to sign a written informed consent document.
• Participants 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.
• Participants 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.
• Participants underwent a total mastectomy, skin-sparing mastectomy, nipple-sparing mastectomy, or a lumpectomy.
• For participants who undergo a lumpectomy, the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS 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.
• a. Participants with margins positive for LCIS are eligible without additional resection.
• For participants who undergo mastectomy, the margins must be free of residual gross tumor.
• a. Participants with microscopic positive margins are eligible if post mastectomy RT of the chest wall will be administered.
• Participants 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: Men or premenopausal women with T1-3N1-2. Postmenopausal women with T3N1 or T1-3N2 diseases.
• The tumor must be ER-positive (≥ 10%), HER2-negative, by current ASCO/CAP guidelines based on testing results. HER2-negative breast cancer is defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0 or 1+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required to confirm the participant's HER2-negative status (based on the most recently analyzed tissue sample tested by a local laboratory).
• Oncotype Dx Recurrence Score must be 0 - 25.
• Participants with known menopausal status at the time of screen.
• a. Postmenopausal status is defined as: i. Participant underwent bilateral oophorectomy, or ii. Age ≥ 60 years, or Age \< 60 years and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene or ovarian suppression) and Folliclestimulating hormone (FSH) and plasma estradiol are in the postmenopausal ranges per local normal ranges. Note: All women who do not meet the criteria for postmenopausal status are considered premenopausal for the purpose of this trial.
• The interval between the last surgery for breast cancer (including re-excision of margins) and screening must be no more than 16 weeks.

You may not qualify if:

• Definitive clinical or radiologic evidence of distant metastases of breast cancer beyond regional lymph nodes (stage IV according to AJCC 8th edition) and/or evidence of recurrence after curative surgery.
• T4 tumors, including inflammatory breast cancer.
• N3 tumors.
• Participants that have received neoadjuvant chemotherapy or biotherapy.
• Participant has received prior treatment with tamoxifen, raloxifene or AIs for reduction in risk ("chemoprevention") of breast cancer and/or treatment for osteoporosis within the last two years prior to randomization. Participant is concurrently using hormone replacement therapy.
• Participants with a known hypersensitivity to any of the excipients of ribociclib and/or ET (e.g. rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption, and soy allergy).
• History of ipsilateral or contralateral invasive breast cancer: Participants with synchronous and/or previous ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) are eligible. If prior ipsilateral DCIS was treated with lumpectomy and radiation therapy, a mastectomy must have been performed for the current cancer.
• Participant has received any CDK4/6 inhibitor.
• Participant has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within two years before randomization. Note: Participants with adequately treated basal or squamous cell skin carcinoma or curatively resected cervical cancer in situ are eligible.
• Participant has known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (testing is not mandatory, unless required by local regulation).
• Life expectancy of \<10 years due to co-morbid conditions in the opinion of the treating investigator.
• Non-epithelial breast malignancies such as sarcoma or lymphoma.
• Hormonally based contraceptive measures must be discontinued prior to registration (including progestin/progesterone IUDs).
• Pregnancy or lactating women or women who plan to become pregnant or breast-feed during the trial.
• a. Note: Pregnancy testing according to institutional standards for women of childbearing potential must be performed at screening.

Sponsors & Collaborators

• Yale University: lead
• Novartis: collaborator
• Breast Cancer Research Foundation: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06511, United States

RECRUITING

MeSH Terms

Interventions

ribociclib; Letrozole; Anastrozole; Goserelin; Chemotherapy, Adjuvant

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Jing Du

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephanie Ladd

CONTACT

954-895-0576; stephanie.ladd@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2025
• First Posted: May 1, 2025
• Study Start: July 9, 2025
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)