Recruiting
Impact of Omitting Chemo Based on Patient's Selection for ER-Positive, HER2-Negative Breast Cancer With Ribociclib and Endocrine Therapy
This is a Phase II, two-arm, single center, patient preference study designed to evaluate the impact of omitting adjuvant chemotherapy in moderate to high-anatomical risk, low-genomic risk (men or premenopausal women T2-3N0 and RS 16-25, or T1-3N1-2 and RS ≤ 25, and postmenopausal women T2-3N0 and RS 26-30, or T1-3N1 and RS 26-30, or T1-3N2 and RS ≤ 25),
ClinicalTrials.gov IDNCT06953882
PhasePHASE2
Enrollment140
SponsorYale University
Age18 Years and older
SexALL
About this study
This is a Phase II, two-arm, single center, patient preference study designed to evaluate the impact of omitting adjuvant chemotherapy in moderate to high-anatomical risk, low-genomic risk (men or premenopausal women T2-3N0 and RS 16-25, or T1-3N1-2 and RS ≤ 25, and postmenopausal women T2-3N0 and RS 26-30, or T1-3N1 and RS 26-30, or T1-3N2 and RS ≤ 25),
Interventions
- Drug: Ribociclib 400mg — 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).
- Drug: Letrozole 2.5mg — 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.
- Drug: Anastrazole 1mg — 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.
- Drug: Goserelin 3.6 MG — 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.
- Radiation: Adjuvant chemotherapy — Adjuvant chemotherapy dose modifications in Arm 2 will be per institutional guidelines and investigator discretion.
Primary outcomes
- Discontinuation rate of ribociclib in patients with resected moderate to high-anatomical risk, low-genomic risk, ER-positive, HER2-negative breast cancer (Within one year of treatment)
Eligibility information
Inclusion Criteria:
1. Female or male age ≥ 18 years old and have the ability to understand and the willingness to sign a written informed consent document.
2. 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.
3. 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.
4. Participants underwent a total mastectomy, skin-sparing mastectomy, nipple-sparing mastectomy, or a lumpectomy.
5. Participants must have undergone axillary staging with sentinel node biopsy (SNB), targeted axillary dissection (TAD), or axillary lymph node dissection (ALND).
6. The following staging criteria must be met postoperatively according to AJCC 8th edition criteria: men or premenopausal women T2-3N0 and RS 16-25, or T1-3N1-2 and RS ≤ 25, and postmenopausal women T2-3N0 and RS 26-30, or T1-3N1 and RS 26-30, or T1-3N2 and RS ≤ 25.
7. 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).
8. 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 Follicle-stimulating 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.
9. HIV-infected participants with undetectable viral load within 6 months and in long term anti-retroviral therapy that would not have a significant drug-drug interaction with ribociclib are eligible for this trial.
10. Radiation therapy should be used according to standard guidelines.
11. Participants must have an ECOG performance status of 0 to 1 within 28 days prior to registration of the study.
12. Participant is able to swallow oral medications.
13. Participants must have adequate organ and marrow function as defined below. All laboratory values must be obtained within 28 days prior to registration of the study.
1. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L.
2. Platelets ≥ 100 × 109/L.
3. Hemoglobin ≥ 9.0 g/dL.
4. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m2 according to the Modification of Diet in Renal Disease (MDRD) formula.
5. Alanine transaminase (ALT) \< 2.5 × Upper Limit Normal (ULN).
6. Aspartate transaminase (AST) \< 2.5 × ULN.
7. Total serum bilirubin \< ULN; or total bilirubin ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN in patients with well documented Gilbert's Syndrome.
8. Patient must have the following laboratory values within normal limits or corrected to within normal limits with supplements (the local laboratory value should be documented within normal limits after the correction) before enrollment:
* Potassium.
* Magnesium.
* Total Calcium (corrected for serum albumin).
14. Standard 12-lead ECG values assessed as: QTcF interval (using Fridericia's correction) at screening \< 450 msec. Resting heart rate 50-90 beats per minute (determined from the ECG).
15. Participant must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.
16. Participants must adhere to the following reproductive and contraceptive requirements while on study treatment and within three months after receiving the last dose of the treatment drugs.
a. General requirements: i. Participants must not be pregnant or breastfeeding. ii. Participants must not donate or freeze eggs for future use related to assisted reproduction during the course of this study or within three months after receiving the last dose of the treatment drugs.
b. For participants of childbearing potential: i. A participant of childbearing potential is defined as an individual who is premenopausal and capable of becoming pregnant. This includes individuals using contraception, those who are sexually inactive, and those with partners who have undergone a vasectomy. A participant is considered of childbearing potential if they have reached menarche, have not yet met the criteria for postmenopause (defined as more than 12 consecutive months of amenorrhea without any other medical cause), and have not undergone surgical sterilization (such as hysterectomy or oophorectomy).
ii. A negative highly sensitive serum pregnancy test (for β-hCG) must be obtained within two weeks of starting the treatment drug administration.
iii. Participants must practice at least one highly effective method of contraception.
c. Highly effective methods of contraception include, but are not limited to: i. Total abstinence (no sexual relations), when this is in line with your preferred and usual lifestyle. Periodic abstinence like calendar, ovulation, symptothermal, post-ovulation methods, and withdrawal are not acceptable methods of contraception.
ii. Total hysterectomy (surgical removal of the uterus and cervix) or tubal ligation (getting your "tubes tied") at least six weeks before taking study treatment.
iii. Your male partner has already been sterilized with the appropriate documentation. The sterilized male partner should be your sole partner.
iv. Placement of an intrauterine device (IUD) v. The use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception or intrauterine system (IUS) or any other form of hormonal contraception (e.g., hormone vaginal ring, hormonal-based IUD or transdermal hormone contraception) is not allowed in this study.
17. Participant has no contraindication for the adjuvant ET in the trial and is planned to be treated with ET for five years or more.
Exclusion Criteria:
Participants who meet any of the following criteria will be excluded from study entry:
1. 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.
2. T4 tumors, including inflammatory breast cancer.
3. N3 tumors.
4. Participants that have received neoadjuvant chemotherapy or biotherapy.
5. Participant is concurrently using hormone replacement therapy.
6. 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).
7. Participant has received any CDK4/6 inhibitor.
8. Participant has a concurrent invasive malignancy or a prior invasive malignancy that requires systemic therapy or place them at more than minimal risk of mortality in the next 5 years.
9. Participant has known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (testing is not mandatory, unless required by local regulation).
10. Life expectancy of \<5 years due to co-morbid conditions in the opinion of the treating investigator.
11. Non-epithelial breast malignancies such as sarcoma or lymphoma.
12. Hormonally based contraceptive measures must be discontinued prior to registration (including progestin/progesterone IUDs).
13. Pregnancy or lactating women or women who plan to become pregnant or breast-feed during t
Study locations
- Yale University, New Haven, Connecticut 06511 United States
Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.
Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-10-22.