Neoadjuvant Dalpiciclib Plus Letrozole for HR+/HER2- Breast Cancer

Neoadjuvant Dalpiciclib Plus Letrozole for HR+/HER2- Breast Cancer: A Single Arm, Open Label, Phase II Trial

In this single arm, open label, phase 2 trial, operable patients with stage IIB-III HR+/HER2- breast cancer will be enrolled and receive six cycles of adjuvant dalpiciclib plus letrozole. This study aims to assessed the biological effects and safety of dalpiciclib in combination with letrozole for HR+/HER2- breast cancer in the neoadjuvant setting.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: dalpiciclib plus letrozole

Detailed Description

This is a single arm, open label, phase 2 trial aimed to investigate the biological effects and safety of neoadjuvant dalpiciclib in combination with letrozole for HR+/HER2- breast cancer. A total of 35 patients with stage IIB-III HR+/HER2- breast cancer will be enrolled. Six 4-week cycles of adjuvant therapy will be administrated. In each cycle, patients use dalpiciclib orally, 150mg, day 1-21, and letrozole orally, 2.5 mg, day 1-28. Premenopausal or perimenopausal patients should combine ovarian function suppression, including bilateral oophorectomy or treatment with gonadotropin-releasing hormone agonists. The primary endpoint is complete cell-cycle arrest at C1D15, defined as ki67≤2.7%. The secondary endpoints include residual cancer burden, overall response rate, change in Ki67 from baseline to 2 weeks of treatment, preoperative endocrine prognostic index, pathologic complete response, breast-conserving surgery rate and safety profile.

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria： Postmenopausal, premenopausal or perimenopausal women aged ≥18. Postmenopausal was defined as: 1) received bilateral oophorectomy, or aged ≥60; 2) aged <60, reached natural menopause (defined as no menses for 12 or more consecutive months with no other reason for the amenorrhea), and with postmenopausal E2 and FSH level; 3) premenopausal or perimenopausal women may also be enrolled as long as they are willing to receive LHRH agonist therapy during the study； Operable patients with ER+ (>10%), HER2- invasive breast carcinomas, regardless of PR level. HER2- was defined as IHC score of 0+, or IHC score of 2+ with negative ISH (amplification ratio <2.0) according to 2018 ASCO-CAP guideline； Untreated patients with stage IIB-III according to AJCC criteria (8th edition)； Without known hypersensitivity to the study drug or its excipients； A ECOG PS score of 0-1； With the ability to swallow the study drug； With sufficient organ function, including 1) bone marrow function: ANC ≥ 1.5 x 109/L (without growth factors within 14 days); PLT ≥ 100 x 109/L (without corrective therapy within 7 days); Hb ≥ 100 g/L (without corrective therapy within 7 days); 2）liver and kidney function: TBIL ≤ ULN; ALT and AST ≤ 3 × ULN (ALT and AST ≤ 5 × ULN for those with liver metastases); BUN and Cr ≤ 1.5×ULN, and creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula); 3) QT interval ≤ 480 ms from the 12-lead electrocardiogram； Able to undergo all puncture biopsies required by the protocol； Volunteered to participate in this study; signed informed consent; with good compliance and willingness to follow-up；

Exclusion Criteria： Previously treated patients, including chemotherapy, radiotherapy, targeted therapy or endocrine therapy, etc.； Concurrently receiving any anti-tumor treatments other than that prescribed by the protocol； Patients with bilateral breast cancer, inflammatory breast cancer or occult breast cancer； Patients with stage IV breast cancer； Patients with severe liver, kidney, or heart dysfunction； Inability to swallow, with chronic diarrhea, with intestinal obstruction, or with other factors affecting drug administration and absorption； Participated in other clinical trials within 4 weeks before enrollment； Known hypersensitivity to the study drug or its excipients; history of ；immunodeficiency, including HIV positive, HCV positive, active viral hepatitis B, other acquired or congenital immunodeficiency diseases, or a history of organ transplantation； History of any cardiac disease, including: 1) arrhythmias requiring drug treatment or of clinical significance; 2) myocardial infarction; 3) heart failure; 4) any other cardiac disease to be inappropriate for this trial judged by the investigator； Women who are pregnant or breastfeeding, women of childbearing potential who test positive for pregnancy test at baseline, or women of childbearing potential who are unwilling to use effective contraception during the study； With serious concomitant disease that endanger safety, or interferes with the ability to complete the study judged by the investigator (including, but not limited to, uncontrolled hypertension, severe diabetes, active infection, etc.)； History of neurological or psychiatric disorders, including epilepsy or dementia; or any other condition inappropriate for this study deemed by the investigator.

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: cohort 1; patients with stage IIB-III HR+/HER2- breast cancer	Drug: dalpiciclib plus letrozole; Six 4-week cycles of dalpiciclib orally, 150mg, day 1-21, and letrozole orally, 2.5 mg, day 1-28; Other Names: D+L

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete cell-cycle arrest at C1D15, defined as ki67≤2.7%	From the date into this study(signed ICF) to C1D15,defined as ki67≤2.7%	up 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
residual cancer burden	The percentage of residual tumors after neoadjuvant therapy is assessed according to breast tumor bed tumors and regional lymph nodes	up 2 years
objective response rate	The rate of CR and PR,determined using RECIST v1.1 criteria	up 2 years
change in Ki67 from baseline to 2 weeks of treatment	change in Ki67 from baseline（From the date into this study(signed ICF) ） to 2 weeks of treatment	up 2 years
preoperative endocrine prognostic index	Prognostic indicators of preoperative endocrine therapy, including mass size after neoadjuvant endocrine therapy, lymph node status, ki67 levels, and estrogen receptor (ER) status	up 2 years
pathologic complete response	After neoadjuvant therapy, there are no residual invasive tumors in the primary focus and regional lymph nodes of breast cancer, but ductal carcinoma in situ may be present(ypT0/is ypN0)	up 2 years
breast-conserving surgery rate	The number of cases that actually underwent breast-conserving surgery after surgery accounted for the percentage of all breast cancer patients who underwent surgery	up 2 years
safety profile	Adverse events (AE) and severe adverse events (SAEs) are recorded. Refer to NCI-CTC AE 5.0 standard	up 2 years

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Qingdao University
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2022
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: August 18, 2022
• First Submitted That Met QC Criteria: August 21, 2022
• First Posted (Actual): August 23, 2022

Study Record Updates

• Last Update Posted (Actual): August 23, 2022
• Last Update Submitted That Met QC Criteria: August 21, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: breast cancer; letrozole; hormone receptor-positive; endocrine therapy; CDK4/6 inhibitor; dalpiciclib
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole
• Other Study ID Numbers: MA-BC-Ⅱ-040

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No