Trial Title:
Efficacy and Safety of Dalpiciclib Plus Toremifene in the Treatment of Advanced First-line HR Positive and HER2 Negative Breast Cancer: a Multicenter, Single Arm, Exploratory Phase II Clinical Study
NCT ID:
NCT06495515
Condition:
CANCER
BRAEST CANCER
Late Frontline
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Dalpiciclib，Toremifen
Description:
1. Dalpiciclib : 150mg orally, once a day, taken for 3 weeks, stopped for 1 week, with
a cycle of 4 weeks. It is recommended to take medication at the same time every day,
with warm water for delivery. It is recommended to do so on an empty stomach and
fast for at least 1 hour before and after taking the medication.
2. Toremifen: 60mg orally, once a day If it is a premenopausal or perimenopausal
patient, it is necessary to combine with OFS (OFS includes bilateral ovariectomy or
GnRHa drugs).
Arm group label:
Treatment group
Summary:
Experimental population:Advanced first-line HR+, HER2 metastatic breast cancer patients
Research endpoint:
Main research endpoint:
PFS evaluated by researchers (according to RECIST 1.1 standard)
Secondary study endpoint:
ORR、CBR、DCR、OS The incidence of adverse events (AE) and severe adverse events (SAE)
Exploratory study endpoint:
Tumor infiltrating lymphocytes (sTIL) Peripheral blood lymphocyte ratio Distribution of
fecal microbiota Research overall design:This study adopts a prospective, single arm
design, and plans to include 36 postmenopausal or premenopausal/perimenopausal patients
with metastatic breast cancer who are HR positive and HER2 negative, and receive
maintenance treatment with darcy plus toremifene. In this study, the screening period did
not exceed 28 days. After completing the screening examination and evaluation, eligible
subjects entered the study treatment period and received maintenance treatment with
darcilib combined with toremifen, for a period of 4 weeks until disease progression,
intolerable toxicity, withdrawal of informed consent, or termination of medication as
determined by the investigator. Conduct research according to the plan regulations
Treatment and visits. Perform tumor imaging evaluation every 2 cycles (8 weeks ± 7 days)
during the first 13 treatment cycles (52 weeks) of the treatment period; Afterwards,
tumor imaging evaluation will be conducted every 3 cycles (12 weeks ± 7 days). Subjects
should visit the research center at the end of treatment/withdrawal from the study to
complete corresponding safety checks and imaging evaluations; And visit the research
center 28 days after the last treatment to complete the corresponding safety assessment.
Detailed description:
Inclusion Criteria :
Participants must meet all of the following inclusion criteria in order to be enrolled in
this trial:
1. Postmenopausal or premenopausal/perimenopausal female patients aged ≥ 18 years and ≤
75 years old,
Meet one of the following conditions:
a) Previously underwent bilateral oophorectomy, or aged ≥ 60 years old; or b)
Age<60, natural postmenopausal state (defined as spontaneous cessation of regular
menstruation for at least 12 consecutive months without any other pathological or
physiological reasons), E2 and FSH at postmenopausal levels.
c) Premenopausal or perimenopausal female patients can also be selected, but they
must be willing to receive LHRH agonist treatment during the study period.
2. ECOG PS 0-1；
3. Female breast cancer patients diagnosed as HR positive and HER2 negative by
pathology have evidence of local recurrence or metastasis, which is not suitable for
surgical resection or radiotherapy for the purpose of cure.
It has been diagnosed as HR positive and HER2 negative breast cancer (ER and PR ≥ 10%)
HER2 is negative. If HER2 is expressed as 2+, in situ hybridization testing is required
to confirm that the HER2 gene has not been amplified; 4. The patient's previous
endocrine therapy must meet the following conditions:
A) Late stage: did not receive any endocrine therapy; Progression within 12 months of
receiving other endocrine treatments (except tamoxifen) in the late stage; b) Stage of
adjuvant endocrine therapy: Progress over 12 months after completion of tamoxifen
assisted endocrine therapy; During the use of aromatase inhibitors (treatment duration
exceeding 6 months) or after completion of treatment, progress may occur.
According to the RECIST 1.1 standard, there should be at least one measurable lesion
present or only bone metastases (including osteolytic lesions or mixed
osteolytic/osteogenic lesions).
6. The functional level of organs must meet the following requirements:
1. Blood routine
•ANC≥1.5×109/L；
•PLT≥90×109/L；
•Hb≥90 g/L；
2. Blood biochemistry
- TBIL≤1.5×ULN； ALT and AST ≤ 2 × ULN;
- BUN and Cr ≤ 1.5 × ULN with creatinine clearance rate ≥ 50 mL/min (Cockcroft
Gault formula);
3. Cardiac color Doppler ultrasound
•LVEF≥50%；
4. 12 lead electrocardiogram The QT interval (QTcF) corrected by the Fridericia method
is<470 ms for females.
7. Patients with negative serum pregnancy test and potential fertility must agree to
use it during treatment and on the last attempt Use effective non hormonal
contraceptive methods for at least 12 months after the trial drug.
8. Voluntarily participate in this study, sign informed consent, have good compliance,
and are willing to cooperate with follow-up.
Exclusion criteria:
1. The previous pathological diagnosis was HER2 positive breast cancer.
2. Researchers determine patients who are not suitable for endocrine therapy. This
includes late stage patients who have symptoms, have spread to the internal organs,
and are at risk of life-threatening complications in the short term (including
patients with uncontrollable exudates (chest, pericardium, abdominal cavity) through
drainage or other methods, pulmonary lymphangitis, and more than 50% liver
involvement).
3. The patient has undergone major surgical procedures unrelated to breast cancer
within 4 weeks before enrollment, or has not fully recovered from such surgical
procedures.
4. Patients with extensive advanced/metastatic, symptomatic visceral diseases, or known
uncontrolled or symptomatic brain metastases.
5. Previously used any CDK inhibitors, tamoxifen, everolimus, or drugs that inhibit the
PI3K mTOR pathway for treatment. Using strong or moderate CYP3A4 and/or CYP2D6
inhibitors or inducers.
6. Other malignant tumors within the past 5 years, excluding cured cervical carcinoma
in situ, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin.
7. Have suffered from any heart disease, including: (1) angina pectoris; (2)
Arrhythmias that require medication treatment or have clinical significance; (3)
Myocardial infarction; (4) Heart failure; (5) Any other heart disease determined by
the researcher as unsuitable for participation in this trial.
8. Inability to swallow, intestinal obstruction, or other factors that affect
medication administration and absorption.
9. Known to be allergic to darcilib, letrozole, or any excipients.
10. Pregnant and lactating female patients, female patients with fertility and positive
baseline pregnancy test results, or female patients of childbearing age who are
unwilling to take effective contraceptive measures throughout the trial period.
11. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem
cell transplantation.
12. There are other serious physical or mental illnesses or laboratory test
abnormalities that may increase the risk of participating in the study, interfere
with the research results, and any other circumstances that the researcher deems
unsuitable for participation in this study.
Termination of treatment criteria:
1. Discovering unexpected, significant, or unacceptable risks to the subjects;
2. During the execution of the experiment, significant errors were found in the plan;
3. The research drug/trial treatment is ineffective, or continuing the trial is
meaningless;
4. Due to factors such as severe delay in subject selection or frequent protocol
deviations, it is extremely difficult to complete the experiment;
5. The subjects experienced severe adverse events, which were intolerable and could not
be relieved;
6. The subject decides to withdraw on their own;
7. The subjects have poor compliance with the research protocol;
Trial medication/treatment:
1. Dalpiciclib : 150mg orally, once a day, taken for 3 weeks, stopped for 1 week, with
a cycle of 4 weeks. It is recommended to take medication at the same time every day,
with warm water for delivery. It is recommended to do so on an empty stomach and
fast for at least 1 hour before and after taking the medication.
2. Toremifen: 60mg orally, once a day If it is a premenopausal or perimenopausal
patient, it is necessary to combine with OFS (OFS includes bilateral ovariectomy or
GnRHa drugs).
The subjects will be treated according to the study protocol until disease progression,
intolerable toxicity, withdrawal of informed consent, or termination of medication as
determined by the researcher 8. Disease progression.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Postmenopausal or premenopausal/perimenopausal female patients aged ≥ 18 years and ≤
75 years old,
Meet one of the following conditions:
a) Previously underwent bilateral oophorectomy, or aged ≥ 60 years old; or b)
Age<60, natural postmenopausal state (defined as spontaneous cessation of
regular menstruation for at least 12 consecutive months without any other
pathological or physiological reasons), E2 and FSH at postmenopausal levels.
c) Premenopausal or perimenopausal female patients can also be selected, but they
must be willing to receive LHRH agonist treatment during the study period.
2. ECOG PS 0-1；
3. Female breast cancer patients diagnosed as HR positive and HER2 negative by
pathology have evidence of local recurrence or metastasis, which is not suitable for
surgical resection or radiotherapy for the purpose of cure.
It has been diagnosed as HR positive and HER2 negative breast cancer (ER and PR ≥ 10%)
HER2 is negative. If HER2 is expressed as 2+, in situ hybridization testing is required
to confirm that the HER2 gene has not been amplified; 4. The patient's previous
endocrine therapy must meet the following conditions:
A) Late stage: did not receive any endocrine therapy; Progression within 12 months of
receiving other endocrine treatments (except tamoxifen) in the late stage; b) Stage of
adjuvant endocrine therapy: Progress over 12 months after completion of tamoxifen
assisted endocrine therapy; During the use of aromatase inhibitors (treatment duration
exceeding 6 months) or after completion of treatment, progress may occur.
According to the RECIST 1.1 standard, there should be at least one measurable lesion
present or only bone metastases (including osteolytic lesions or mixed
osteolytic/osteogenic lesions).
6. The functional level of organs must meet the following requirements:
1. Blood routine
•ANC≥1.5×109/L；
•PLT≥90×109/L；
•Hb≥90 g/L；
2. Blood biochemistry
- TBIL≤1.5×ULN； ALT and AST ≤ 2 × ULN;
- BUN and Cr ≤ 1.5 × ULN with creatinine clearance rate ≥ 50 mL/min (Cockcroft
Gault formula);
3. Cardiac color Doppler ultrasound
•LVEF≥50%；
4. 12 lead electrocardiogram The QT interval (QTcF) corrected by the Fridericia method
is<470 ms for females.
7. Patients with negative serum pregnancy test and potential fertility must agree to
use it during treatment and on the last attempt Use effective non hormonal
contraceptive methods for at least 12 months after the trial drug.
8. Voluntarily participate in this study, sign informed consent, have good compliance,
and are willing to cooperate with follow-up.
Exclusion Criteria:
1. The previous pathological diagnosis was HER2 positive breast cancer.
2. Researchers determine patients who are not suitable for endocrine therapy. This
includes late stage patients who have symptoms, have spread to the internal organs,
and are at risk of life-threatening complications in the short term (including
patients with uncontrollable exudates (chest, pericardium, abdominal cavity) through
drainage or other methods, pulmonary lymphangitis, and more than 50% liver
involvement).
3. The patient has undergone major surgical procedures unrelated to breast cancer
within 4 weeks before enrollment, or has not fully recovered from such surgical
procedures.
4. Patients with extensive advanced/metastatic, symptomatic visceral diseases, or known
uncontrolled or symptomatic brain metastases.
5. Previously used any CDK inhibitors, tamoxifen, everolimus, or drugs that inhibit the
PI3K mTOR pathway for treatment. Using strong or moderate CYP3A4 and/or CYP2D6
inhibitors or inducers.
6. Other malignant tumors within the past 5 years, excluding cured cervical carcinoma
in situ, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin.
7. Have suffered from any heart disease, including: (1) angina pectoris; (2)
Arrhythmias that require medication treatment or have clinical significance; (3)
Myocardial infarction; (4) Heart failure; (5) Any other heart disease determined by
the researcher as unsuitable for participation in this trial.
8. Inability to swallow, intestinal obstruction, or other factors that affect
medication administration and absorption.
9. Known to be allergic to darcilib, letrozole, or any excipients.
10. Pregnant and lactating female patients, female patients with fertility and positive
baseline pregnancy test results, or those in the whole family Female patients of
childbearing age who were unwilling to take effective contraceptive measures during
the trial period.
11. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem
cell transplantation.
12. Other serious physical or mental illnesses or laboratory test abnormalities may
increase the risk of participating in the study, or Disturb the research results and
any other circumstances that the researcher deems unsuitable for participation in
this study.
Gender:
Female
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
August 1, 2024
Completion date:
June 30, 2026
Lead sponsor:
Agency:
Tianjin Medical University Cancer Institute and Hospital
Agency class:
Other
Source:
Tianjin Medical University Cancer Institute and Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06495515
