A Clinical Study of Darcilil Combined With AI Combined With Pyrrotinib in the Treatment of TPBC

January 31, 2024 updated by: Second Affiliated Hospital of Soochow University

Prospective, Single-arm, Single-center Clinical Study of Darcilil Combined With AI Combined With Pyrrotinib in the Treatment of Elderly Advanced Triple-positive Breast Cancer.

Elderly patients with advanced triple-positive breast cancer have the characteristics of low physical status and poor treatment tolerance. Therefore, such patients are often unable to tolerate more toxic chemotherapy regimen, and it is particularly important to choose a highly effective and low-toxic treatment regimen. However, few studies have paid attention to the treatment of such patients in the past.

Pyrrotinib is a small molecule, irreversible, panerbb receptor tyrosine kinase inhibitor, which was independently developed by our country and has shown excellent efficacy in second-line anti-HER2 treatment of breast cancer, and has become the second-line standard treatment choice for advanced HER2-positive breast cancer. In addition, PHILA study results showed that the mPFS of pyrrotinib group reached 24 months. Compared with the control group, the duration of 10 months was significantly extended, indicating the significant efficacy of pyrrotinib in the first-line treatment of advanced HER2-positive breast cancer.

Darsili is a CDK4/6 inhibitor independently developed in China, which has been reconstructed and optimized in molecular structure, and has become a new CDK4/6 inhibitor with more powerful modification by introducing piperidine structure through replacement of classical electronic and other panbody. The results of DAWNA-2 study indicated that the mPFS of Dalsily combined AI group reached 30.6 months, which was significantly longer than 18.2 months of the control group, and was the longest in similar studies.

MUKDEN01 study, for the first time, tried the efficacy of pyrrotinib + letrozole + Dalsily regimen in the new adjuvant therapy of TPBC patients, and the results showed that ORR reached 87.4%, CR rate was 30.4%, and pCR rate was 35.4%. Therefore, to further confirm the efficacy and safety of this protocol in elderly patients with advanced triple positive breast cancer, we intend to conduct this study. This is a prospective, single-arm, single-center clinical trial in which participants were treated with darcilide +AI (letrozole/anastrozole/exemestane) + pyrrotinib until disease progression, toxicity became intolerable, informed consent was withdrawn, or investigator judgment required discontinuation. The successful development of this study provides a new direction for the first-line treatment of elderly advanced triple-positive breast cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In this open design, single-arm, single-center, prospective clinical study, 28 elderly patients with triple-positive advanced breast cancer were planned to receive treatment with darcilil combined with pyrrotinib and AI until the disease progressed, toxicity became intolerable, informed consent was withdrawn, or the investigator judged that the drug must be discontinued. The main objective of this study was to observe the safety and efficacy of Dalcilil combined with pyrrotinib and AI in the treatment of triple-positive senile advanced breast cancer.

In this study, the screening period did not exceed 28 days, and qualified subjects entered the study treatment period (every 28 days is a treatment cycle) after completing the screening examination and evaluation, and conducted the study treatment and visit according to the protocol. Imaging evaluation was performed according to the clinical routine during the study treatment. The imaging evaluation could be carried out according to the RECIST 1.1 standard, and the evaluation result of the investigator was the final result. At the end of treatment/withdrawal from the study, subjects should visit the research center to complete the corresponding safety check and imaging evaluation; In addition, a visit to the research center was conducted 28 days after the last treatment to complete the corresponding safety assessment.

Safety follow-up: the subjects were followed up until the initiation of other antineoplastic drugs. All AE recovered to grade 0-1 or baseline levels or died, whichever was achieved first.

Efficacy follow-up: All subjects were required to be followed until tumor progression or death or withdrawal of informed consent, whichever came first.

Follow-up for survival: All subjects were followed for survival until death or withdrawal of informed consent or the end of the trial, whichever came first.

Study Type

Interventional

Enrollment (Estimated)

34

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Jiangsu
      • Suzhou, Jiangsu, China, 215000
        • Recruiting
        • The Second Affiliated Hospital of Soochow University
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 1.Age: ≥65 years old; 2. Histologically confirmed stage IV TPBC; 3. Without prior treatment, adjuvant endocrine therapy and anti-HER2 therapy should be completed for more than one year; 4.TPBC is defined as HER2-positive (3+ by immunohistochemistry, or 2+ by fluorescence in situ hybridization), ER-positive (more than 10% of tumor cells expressed estrogen receptor by immunohistochemistry), and PR-positive (at least 1% of tumor cells expressed progesterone receptor by immunohistochemistry) breast cancer; 5.ECOG score is 0-3 points; 6. Expected survival ≥12 weeks; 7. Normal function of major organs:

    1. Blood routine:

      Neutrophil (ANC) ≥1.5×109/L; Platelet count (PLT) ≥75×109/L; Hemoglobin (Hb) ≥90 g/L;

    2. Blood biochemistry:

      Total bilirubin (TBIL) ≤1.5× upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0×ULN; Alkaline phosphatase ≤2.5×ULN; Urea or urea nitrogen (BUN) and creatinine (Cr) ≤1.5×ULN;

    3. Heart color ultrasound:

Left ventricular ejection fraction (LVEF) ≥50%.

Exclusion Criteria:

  • 1. Breast cancer with no evaluable lesions such as inflammation or occult; 2. Other malignancies within five years 3. Received other tyrosine kinase inhibitors, anti-HER2 treatment and T-DM1 treatment less than one year ago; 4. Patients with intestinal obstruction or fasting, gastrointestinal history, with diarrhea as the main symptom; 5. Suffering from mental illness or psychotropic substance abuse, unable to cooperate; 6. Pregnant or lactating women; 7. Participants considered unsuitable for inclusion by the researchers.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment group
Dalcilib +AI (letrozole/anastrozole/exemestane) + pyrrolizinib
Drug: Darcilide +AI (letrozole/anastrozole/Exemestane) + pyrrotinib

Darcilie: 125mg orally once a day, taken for 21 days and stopped for 7 days, 28 days as a cycle.

AI: Letrozole: 2.5mg orally once daily, or anastrozole 1mg orally once daily, or exemestane 25mg orally once daily.

Pyrrotinib: Initial dose of 240mg in the first week, if diarrhea and other side effects can be tolerated, 320 mg can be added in the second week, once a day, oral administration within 30 minutes after breakfast, 21 days for 1 cycle

All investigational drugs should be used for disease progression or when patients have an intolerable adverse reaction or are withdrawn from the study for other reasons.

Oral pyrrotinib is recommended along with prophylactic antidiarrheal medication. Antidiarrheal regimen 1: Oral imodium (2 tablets/times, 2 times a day) from the first week, 1 tablet, 2 times a day from the second week. Antidiarrheal regimen 2: montmorillonite powder (3 times a day, 1 pack/time)+ whole intestine sheng (3 pills/time 2 times a day).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: 29 months
Defined as the date from enrollment until the first recording of tumor progression (as measured by RECIST 1.1 criteria, regardless of continuation of treatment) or the date of death from any cause, whichever occurs first.
29 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 29 months
From the date of signing the informed consent to the date of death from any cause. For subjects who were still alive at the last follow-up, the OS was deleted based on the last follow-up time. For subjects who were lost to follow-up, the OS was calculated as the last confirmed survival time before the lost follow-up. The OS for data deletion is defined as the time from group entry to deletion.
29 months
Objective Response Rate
Time Frame: 29 months
Proportion of all participants receiving investigational therapy who rated the best overall response (BOR) as complete response to CR or partial response to PR according to RECIST 1.1 criteria.
29 months
Disease Control Rate
Time Frame: 29 months
Optimal proportion of subjects with CR, PR, and SD in overall response.
29 months
Objective Duration Of Remission
Time Frame: 29 months
Defined as the period from the date of first recorded tumor remission (as measured by RECIST 1.1) to the date of first recorded objective tumor progression (as measured by RECIST 1.1) or the date of death from any cause, whichever occurs first.
29 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Second Affiliated Hospital of Soochow University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 1, 2024

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

January 18, 2024

First Submitted That Met QC Criteria

January 31, 2024

First Posted (Estimated)

February 1, 2024

Study Record Updates

Last Update Posted (Estimated)

February 1, 2024

Last Update Submitted That Met QC Criteria

January 31, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LK2023106

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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