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

Sponsor

The Affiliated Hospital of Qingdao University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05512416

Collaborator

Jiangsu HengRui Medicine Co., Ltd. (Industry)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: dalpiciclib plus letrozole	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

35 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

May 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

residual cancer burden [up 2 years]
The percentage of residual tumors after neoadjuvant therapy is assessed according to breast tumor bed tumors and regional lymph nodes
objective response rate [up 2 years]
The rate of CR and PR,determined using RECIST v1.1 criteria
change in Ki67 from baseline to 2 weeks of treatment [up 2 years]
change in Ki67 from baseline（From the date into this study(signed ICF) ） to 2 weeks of treatment
preoperative endocrine prognostic index [up 2 years]
Prognostic indicators of preoperative endocrine therapy, including mass size after neoadjuvant endocrine therapy, lymph node status, ki67 levels, and estrogen receptor (ER) status
pathologic complete response [up 2 years]
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)
breast-conserving surgery rate [up 2 years]
The number of cases that actually underwent breast-conserving surgery after surgery accounted for the percentage of all breast cancer patients who underwent surgery
safety profile [up 2 years]
Adverse events (AE) and severe adverse events (SAEs) are recorded. Refer to NCI-CTC AE 5.0 standard

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.