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

A Single-arm Exploratory Study of the Efficacy and Safety of CDK4/6 Inhibitors in Combination with Endocrine Therapy in the Neoadjuvant Treatment of HR+/HER2- Early Breast Cancer

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer Stage II; Breast Cancer Stage III
• Intervention / Treatment: Drug: Ribociclib; abemaciclib; palbociclib; Dalpiciclib

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hongmei Zheng, Doctor; Phone Number: +86 18971624606; Email: zhenghongmeicj@163.com
• Study Contact Backup: Name: Xinhong Wu, Doctor; Phone Number: +8618971624606; Email: 18971624606@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: HR+/HER2- breast cancer patients who are intolerance or insensitivity to neoadjuvant chemotherapy; Age ≥ 18 years old.; 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).; 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.; ECOG PS score 0-2

Drug: Ribociclib; abemaciclib; palbociclib; Dalpiciclib; Neoadjuvant therapy: CDK4/6 inhibitor combined with endocrine, a total of 6 cycles, 1 cycle every 28 days. CDK4/6 inhibitors (choose one of the following four types): Dalpiciclib 125 mg orally once a day d1-21 every 28 days for a cycle (3 weeks/1 week off); Palbociclib 125 mg orally once a day, d1-21, every 28 days in cycles (3 weeks/1 week off); Abemaciclib 150 mg orally twice daily in 28-day cycles (may be reduced to 100 mg orally twice daily if not tolerated); Ribociclib 400 mg orally once a day in a 28-day cycle Endocrine therapy drugs: take according to the label. Premenopausal patients need to be treated for ovarian function suppression.; Other Names: Letrozole; Anastrozole; Esomeprazole

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ki67 variations	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.	At the end of Cycle 2(each cycle is 28 days)
complete cell cycle arrest (CCCA; Ki67 ≤ 2.7%)	Ki67 levels were assessed through serial biopsies at baseline , before ET treatment and C2D28 after ET treatment	6 months
iDFS	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.	2 years
QoL	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.	1 year

Collaborators and Investigators

• Sponsor: Hongmei Zheng, PhD

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 30, 2024
• First Submitted That Met QC Criteria: February 1, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 14, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: neoadjuvant treatment; HER2 negative; CDK4/6 inhibitors; Hormone receptor (HR) positive
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Protein Kinase Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Estrogen Antagonists; Aromatase Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Letrozole; Anastrozole; Palbociclib; Esomeprazole
• Other Study ID Numbers: HBCHBCC011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Baseline data of enrolled patients, endocrine therapeutics, and idfs

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No