NCT06953882

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

SELECT: A Phase II Adjuvant Trial Evaluating the Impact of Omitting Chemotherapy Based on Patient's Selection for Moderate to High-Anatomical Risk, Low-Genomic Risk, ER-Positive, HER2- Negative Breast Cancer With a Combination Regimen of Ribociclib and Optimized Endocrine Therapy

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 140 (estimated)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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).

Detailed description

Most patients with ER-positive, HER2-negative, node-positive breast cancer are treated with curative intent, which typically involves some combination of surgery, radiation, endocrine therapy (ET) and often chemotherapy. The recent integration of CDK 4/6 inhibitors into adjuvant ET has complicated treatment decision-making for this subtype of breast cancer. These agents have demonstrated substantial benefits in reducing recurrence risk when combined with ET, prompting a reassessment of the role and necessity of chemotherapy in certain patient populations. However, it remains unclear to what extent prior exposure to a course of adjuvant chemotherapy impacts treatment persistence of CDK 4/6 inhibition. In the NATALEE and monarchE trials, approximately 90% of participants received prior chemotherapy, yet 28 - 36% participants discontinued the CDK 4/6 inhibitors prematurely. These findings underscore the significant barrier in maintaining long-term persistence to CDK 4/6 inhibitor therapy and emphasize the need to develop and implement strategies for optimizing treatment regimens to minimize discontinuation rates, especially in patients for whom the benefit of chemotherapy is uncertain. This is a Phase II, two-arm, single center, patient preference clinical trial designed to evaluate the impact of omitting adjuvant chemotherapy on ribociclib treatment persistence in moderate to high-anatomical risk, low-genomic risk (Oncotype DX Recurrence Score, RS ≤ 25), ER-positive, HER2-negative breast cancer participants treated with a combination regimen of ribociclib and optimized endocrine therapy. Eligible participants aged ≥18 years, ECOG PS of 0 to 1, with anatomic stage II/III ER-positive (≥10%), HER2-negative breast cancer (men or premenopausal women with T1-3N1-2 or postmenopausal women with T3N1 or T1-3N2) and RS 0-25 will be included. Participants will have the option to decide whether to include adjuvant chemotherapy in their treatment plan. Arm 1 will receive the combination of ribociclib and optimized ET. Arm 2 will be treated with adjuvant chemotherapy followed by a combination of ribociclib and optimized ET. Optimized ET includes an oral aromatase inhibitor (letrozole or anastrozole) for all participants, with the addition of a GnRH agonist (goserelin) to achieve gonadal suppression in all men and premenopausal women. Key exclusion criteria are distant metastases, T4, N3, neoadjuvant chemotherapy and clinically significant uncontrolled heart disease at screening. The primary objective is to evaluate 1-year discontinuation rate of ribociclib in each arm. Secondary endpoints include 3-year invasive disease-free survival, factors impacting treatment decision, quality of life, decisional regret, and fear of recurrence. Estimated enrollment is 140 participants (70 each arm) to ensure investigators can estimate one-year discontinuation rate with a reasonable level of precision.

Conditions

• HER2 Negative Breast Cancer

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2025-07-09
• Primary completion: 2030-09-01
• Completion: 2030-09-01
• First posted: 2025-05-01
• Last updated: 2025-07-14

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study