Darsilide Combined With AI, Trastuzumab and Patuzumab in the Neoadjuvant Treatment of HR+/HER2+ Breast Cancer

A Clinical Study of Darsilide Combined With AI, Trastuzumab and Patuzumab in the Neoadjuvant Treatment of HR Positive HER2 Positive Breast Cancer

This study is intended to carry out a single arm, prospective, open clinical study, and use Darsilide combined with endocrine therapy, Trastuzumab and Patuzumab to treat early or locally advanced breast cancer of TPBC before surgery. It is intended to further explore the efficacy and safety of the new adjuvant treatment for TPBC patients with step-down therapy.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; HER2-positive Breast Cancer
• Intervention / Treatment: Drug: Dalcilib+letrozole+HP treatment group

Detailed Description

This study is intended to carry out a single arm, prospective, open clinical study, and use Darsilide combined with endocrine therapy, Trastuzumab and Patuzumab to treat early or locally advanced breast cancer of TPBC before surgery. It is intended to further explore the efficacy and safety of the new adjuvant treatment for TPBC patients with step-down therapy.

All participants received 150mg of darcilib once a day. Take it continuously for 21 days, then stop taking it for 7 days, with a treatment cycle of 28 days.Letrozole 2.5mg once daily (premenopausal patients treated with OFS).Trastuzumab (8mg/kg first dose, 6mg/kg sequential) and Patuzumab (840mg first dose, 420mg/kg sequential) were administered intravenously every 3 weeks, or fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (1200 mg pertuzumab plus 600 mg trastuzumab loading dose in 15 mL, followed by 600 mg pertuzumab plus 600 mg trastuzumab maintenance doses in 10 mL), both administered every 3 weeks, with all patients receiving 8 cycles of treatment. After starting treatment and before surgery, subjects will be monitored through breast MRI to evaluate clinical tumor remission. The primary endpoint was the pCR rate in the group receiving darcilib+letrozole+HP treatment, defined as the proportion of patients who achieved pCR after surgery after neoadjuvant therapy.

• Study Type: Interventional
• Enrollment (Estimated): 71
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhenzhen Liu; Phone Number: 0371-65587005; Email: liuzhenzhen73@126.com
• Study Contact Backup: Name: Dechuang Jiao; Phone Number: 0371-65588380; Email: jiaodechuang@163.com

Study Locations

• China
  • Henan
    • Henan, Henan, China, 450008
      • Recruiting
      • Henan cacer hospital
      • Contact: Zhen Liu; Phone Number: 13838308034

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Female initial treatment patients aged ≥ 18 years and ≤ 70 years.
2. ECOG score 0-1 points.
3. Pathologically confirmed as invasive breast cancer, with tumor staging of II-IIIA.
4. HR positive HER-2 positive.
5. The main organs function normally and meet the following standards:

（1）The blood routine examination standards must comply with:ANC ≥1.5×10 9/L；PLT ≥100×109/L；Hb ≥90g/L. （2）Biochemical examination must meet the following standards: TBIL ≤ 1.5 Upper limit of normal value (ULN)；ALT and AST ≤ 1.5 times the upper limit of normal value (ULN)；Alkaline phosphatase ≤ 2.5 times the upper limit of normal value (ULN)；BUN and Cr ≤ 1.5 × ULN and creatinine clearance rate ≥ 50 mL/min； （3）Cardiac ultrasound and echocardiography: Left ventricular ejection fraction (LVEF ≥ 50%).

6. For female patients who have not undergone menopause or surgical sterilization: Agree to abstain or use effective contraceptive methods during the treatment period and at least 7 months after the last administration during the study treatment.

7. Volunteer to join this study and sign an informed consent form.

Exclusion Criteria:

1. Stage IV (metastatic) breast cancer.
2. inflammatory breast cancer.
3. Previously received anti-tumor therapy or radiation therapy for any malignant tumor, excluding cured cervical cancer in situ, basal cell carcinoma, or squamous cell carcinoma.
4. Simultaneously receiving anti-tumor therapies in other clinical trials, including endocrine therapy, bisphosphate therapy, or immunotherapy.
5. The patient had undergone major surgical procedures unrelated to breast cancer within 4 weeks before enrollment, or the patient has not fully recovered from such surgical procedures.
6. Individuals who have previously suffered from clinically significant lung diseases, including but not limited to interstitial pneumonia, pneumonia, pulmonary fibrosis, and radiation pneumonia (excluding radiation changes that do not require corrective treatment), or those who have been found to have such diseases through screening period examinations.
7. Serious heart disease or discomfort, including but not limited to the following diseases:

（1）Confirmed history of heart failure or systolic dysfunction (LVEF<50%). （2）High risk uncontrolled arrhythmia（atrial tachycardia，ventricular tachycardia，Higher level atrioventricular block）； （3）Angina pectoris requiring treatment with anti angina drugs； （4）Clinically significant heart valve disease； （5）ECG shows transmural myocardial infarction； （6）Poor control of hypertension (systolic blood pressure>180 mmHg and/or diastolic blood pressure>100 mmHg)； 8. Inability to swallow, intestinal obstruction, or other factors that affect drug administration and absorption.

9. Individuals with a known history of allergies to the drug components of this protocol；Having a history of immunodeficiency, including HIV testing positive, or suffering from other acquired or congenital immunodeficiency diseases, or having a history of organ transplantation.

10. Pregnant and lactating female patients, those with fertility and positive baseline pregnancy test results, or those of childbearing age who are unwilling to take effective contraceptive measures during the entire trial period and within 7 months after the last study medication.

11. Suffering from severe comorbidities or other comorbidities that may interfere with the planned treatment, or any other situation where the researcher deems the patient unsuitable to participate in this study.

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: Dalcilib+letrozole+HP; All subjects received Dalcilib 150mg qd, stopped for 1 week after 3 weeks，and letrozole (2.5mg qd) (premenopausal combined with OFS). The subjects received 2 cycles of preoperative treatment with darcilib combined with letrozole, trastuzumab, and patstuzumab. Then, MRI efficacy evaluation will be conducted, and patients who achieved PR continue to receive the original treatment regimen for 6 cycles, while those who did not achieve PR switched to the TCHP chemotherapy regimen for 6 cycles.

Drug: Dalcilib+letrozole+HP treatment group; All participants received 150mg of darcilib once a day. Take it continuously for 21 days, then stop taking it for 7 days, with a treatment cycle of 28 days. Letrozole 2.5mg once daily (premenopausal patients treated with OFS); Trastuzumab (8mg/kg first dose, 6mg/kg sequential) and Patuzumab (840mg first dose, 420mg/kg sequential) were administered intravenously every 3 weeks, or fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (1200 mg pertuzumab plus 600 mg trastuzumab loading dose in 15 mL, followed by 600 mg pertuzumab plus 600 mg trastuzumab maintenance doses in 10 mL), both administered every 3 weeks.; Other Names: experimental group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathologic complete response	The proportion of patients in this group who achieved pCR after surgery after neoadjuvant therapy	Immediately after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse event occurrence	The incidence and severity of adverse events (including serious adverse events)	At the end of one Cycle (each cycle is 28 days)
objective response rate	The proportion of patients who achieved CR or PR before surgery after neoadjuvant therapy among all subjects	At the end of Cycle 6 (each cycle is 28 days)
Residual cancer burden	Proportion of patients with residual cancer burden score of 0-1 after surgery	Immediately after surgery
Event free survival	The time interval between enrollment and the first recording of related events, including preoperative disease progression, postoperative disease recurrence, and death from any cause.	5 years after surgery
Disease free survival	The time interval between the first day without disease (surgery date) and the first recording of related events, including postoperative disease recurrence and death from any cause.	5 years after surgery
Distant disease/recurrence free survival	The time interval between the first day without disease ( surgery date) and the first occurrence of distant recurrence.	5 years after surgery

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Investigators: Principal Investigator: Zhenzhen Liu, Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: November 14, 2023
• First Submitted That Met QC Criteria: February 23, 2024
• First Posted (Actual): February 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 12, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: HER2-positive Breast Cancer; Disease-free survival; objective response rate; pathologic complete response; Dalcelli
• 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; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Estrogen Antagonists; Aromatase Inhibitors; Letrozole
• Other Study ID Numbers: HELEN-017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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