The Efficacy and Safety of CDK4/6 Inhibitors in Combination with Endocrine Therapy in the Neoadjuvant Treatment

Not Applicable

Not yet recruiting

• Conditions: Breast Cancer Stage III; Breast Cancer Stage II
• Interventions: Drug: Ribociclib; abemaciclib; palbociclib; Dalpiciclib

• Registration Number: NCT06810492
• Lead Sponsor: Hongmei Zheng, PhD

Brief Summary

To explore the efficacy and safety of CDK4/6 inhibitors combined with endocrine neoadjuvant therapy for stage II-III HR-positive/HER2-negative breast cancer.

This study adopts a single-arm, open-label design, and plans to include 40 patients with stage II-III HR+/HER2- breast cancer.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-30
• Study First Submitted QC: 2025-02-01
• Study First Posted: 2025-02-05
• Last Update Submitted: 2025-03-14
• Last Update Posted: 2025-03-17
• Study Start: 2025-04-01
• Primary Completion: 2025-12-30
• Study Completion: 2027-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Age ≥ 18 years old.
2. Premenopausal and postmenopausal stage II-III females or males (patients with multicenter and/or multifocal early-invasive breast cancer) if all histopathological examination of tumors meet the pathological criteria of ER and/or PR>10% and HER2- (HER2 expression 0 or 1+ or 2+ and negative FISH test).
3. Patients must have histologically confirmed ER and/or PR >10%, HER2-, early invasive breast cancer.
4. Intolerance or insensitivity to neoadjuvant chemotherapy: 2 cycles of neoadjuvant chemotherapy, tumor evaluation PD/SD, advanced age, and inability to tolerate chemotherapy with underlying diseases.
5. ECOG PS score 0-2.
6. Patients must be able and willing to swallow and retain oral medications.
7. Premenopausal women within 14 days of enrollment, or women with amenorrhea for less than 12 months at the time of enrollment, must have a negative serum or urine pregnancy test.
8. Patients who have received neoadjuvant endocrine therapy are eligible for enrollment as long as they are enrolled within 6 months of initial histologic diagnosis and have completed no more than 2 months of neoadjuvant endocrine therapy.
9. Absolute neutrophil count ≥ 1500/µL, platelet ≥ 100000/mm3, hemoglobin ≥ 10g/dL

Exclusion Criteria

1. Prior treatment with any CDK inhibitor.
2. Inflammatory breast cancer or stage IV breast cancer or bilateral breast cancer.
3. History of anaphylaxis caused by chemical or biologic components similar to dalsily.
4. Patients who have received any drugs or substances with effective CYP3A isoenzyme inhibitors or inducers within 7 days of enrollment.
5. Uncontrolled intercurrent illness that would limit compliance with study requirements.
6. Pregnant women or women of childbearing potential with a negative pregnancy test within 14 days prior to admission.
7. Patients with any history of malignancy are not eligible.
8. Patients who have received endocrine therapy within 5 years prior to the diagnosis of the current malignancy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HR+/HER2- breast cancer patients who are intolerance or insensitivity to neoadjuvant chemotherapy	Ribociclib; abemaciclib; palbociclib; Dalpiciclib	1. Age ≥ 18 years old. 2. Premenopausal and postmenopausal stage II-III females or males (patients with multicenter and/or multifocal early-invasive breast cancer) if all histopathological examination of tumors meet the pathological criteria of ER and/or PR\>10% and HER2- (HER2 expression 0 or 1+ or 2+ and negative FISH test). 3. Intolerance or insensitivity to neoadjuvant chemotherapy: 2 cycles of neoadjuvant chemotherapy, tumor evaluation PD/SD, advanced age, and inability to tolerate chemotherapy with underlying diseases. 4. ECOG PS score 0-2

Primary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	At the end of Cycle 6 (each cycle is 28 days)	The main effect evaluation index was Objective response rate (ORR) after CDK4/6 inhibitor combined with endocrine, a total of 6 cycles.

Secondary Outcome Measures

Name	Time	Method
Ki67 variations	At the end of Cycle 2(each cycle is 28 days)	Tumor samples were collected by surgical resection during the screening period (mandatory), at the time of treatment for 8 weeks (mandatory), and at the time of surgery (mandatory). Each test center was responsible for collecting samples, and the Hubei cancer Hospital determined the levels of Ki67.
complete cell cycle arrest (CCCA; Ki67 ≤ 2.7%)	6 months	Ki67 levels were assessed through serial biopsies at baseline , before ET treatment and C2D28 after ET treatment
iDFS	2 years	Disease free survival for 3 years and 5 years, which means the rate of patients without local recurrence and distant metastasis in the whole patients at the same group will be calculated with Kaplan Meier survival curves.
QoL	1 year	Life quality score was evaluated by European Organization of Research and treatment of Cancer-Questionnaire of Life Quality-C30 Version 3 (EORTC-QLQ-C30 V3), which conduct a series of questions about the patients' physical condition, activity of daily life, adverse reaction and mood condition. The range in the questionnaire for the score is from 1 to 4, in which 1 stands for having no discomfort and 4 stands for having great discomfort.