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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05512416
• Other study ID #: MA-BC-?-040
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: August 2022
• Est. completion date: May 2024

Study information

• Verified date: August 2022
• Source: The Affiliated Hospital of Qingdao University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 35
• Est. completion date: May 2024
• Est. primary completion date: August 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• dalpiciclib plus letrozole
Six 4-week cycles of dalpiciclib orally, 150mg, day 1-21, and letrozole orally, 2.5 mg, day 1-28

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
The Affiliated Hospital of Qingdao University	Jiangsu HengRui Medicine Co., Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	objective response rate	The rate of CR and PR,determined using RECIST v1.1 criteria	up 2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	safety profile	Adverse events (AE) and severe adverse events (SAEs) are recorded. Refer to NCI-CTC AE 5.0 standard	up 2 years