Trial Title:
A Clinical Study of Darcilil Combined With AI Combined With Pyrrotinib in the Treatment of TPBC
NCT ID:
NCT06235931
Condition:
Breast Neoplasms
Conditions: Official terms:
Breast Neoplasms
Letrozole
Anastrozole
Exemestane
Conditions: Keywords:
Triple-positive breast cancer
Dalsillie
Pyrrolizinib
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Darcilide +AI (letrozole/anastrozole/Exemestane) + pyrrotinib
Description:
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intolerable adverse reaction or are withdrawn from the study for other reasons.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).
Arm group label:
Treatment group
Summary:
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.
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.
Criteria for eligibility:
Criteria:
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.
Gender:
Female
Gender based:
Yes
Minimum age:
65 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The Second Affiliated Hospital of Soochow University
Address:
City:
Suzhou
Zip:
215000
Country:
China
Status:
Recruiting
Contact:
Last name:
Hui Wang
Phone:
13913501391
Email:
whuisd@163.com
Contact backup:
Last name:
Shushu Zhang
Phone:
18936081534
Email:
xyzss567@163.com
Start date:
February 1, 2024
Completion date:
December 1, 2026
Lead sponsor:
Agency:
Second Affiliated Hospital of Soochow University
Agency class:
Other
Source:
Second Affiliated Hospital of Soochow University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06235931
