Ignite Creation Date:
2024-07-17 @ 10:51 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06495515
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-10
First Post:
2024-07-03
Brief 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
Sponsor:
Tianjin Medical University Cancer Institute and Hospital
Organization:
Tianjin Medical University Cancer Institute and Hospital
Study Overview
Official 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
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Experimental populationAdvanced first-line HR HER2 metastatic breast cancer patients
Research endpoint
Main research endpoint
PFS evaluated by researchers according to RECIST 11 standard
Secondary study endpoint
ORRCBRDCROS 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 designThis study adopts a prospective single arm design and plans to include 36 postmenopausal or premenopausalperimenopausal 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 treatmentwithdrawal 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
Research endpoint
Main research endpoint
PFS evaluated by researchers according to RECIST 11 standard
Secondary study endpoint
ORRCBRDCROS 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 designThis study adopts a prospective single arm design and plans to include 36 postmenopausal or premenopausalperimenopausal 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 treatmentwithdrawal 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 premenopausalperimenopausal 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 Agelt60 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 patient39s 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 11 standard there should be at least one measurable lesion present or only bone metastases including osteolytic lesions or mixed osteolyticosteogenic lesions
6 The functional level of organs must meet the following requirements
1 Blood routine
ANC15109L
PLT90109L
Hb90 gL
2 Blood biochemistry
TBIL15ULN ALT and AST 2 ULN
BUN and Cr 15 ULN with creatinine clearance rate 50 mLmin Cockcroft Gault formula
3 Cardiac color Doppler ultrasound
LVEF50
4 12 lead electrocardiogram The QT interval QTcF corrected by the Fridericia method islt470 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 advancedmetastatic 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 andor 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 drugtrial 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 medicationtreatment
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
Participants must meet all of the following inclusion criteria in order to be enrolled in this trial
1 Postmenopausal or premenopausalperimenopausal 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 Agelt60 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 patient39s 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 11 standard there should be at least one measurable lesion present or only bone metastases including osteolytic lesions or mixed osteolyticosteogenic lesions
6 The functional level of organs must meet the following requirements
1 Blood routine
ANC15109L
PLT90109L
Hb90 gL
2 Blood biochemistry
TBIL15ULN ALT and AST 2 ULN
BUN and Cr 15 ULN with creatinine clearance rate 50 mLmin Cockcroft Gault formula
3 Cardiac color Doppler ultrasound
LVEF50
4 12 lead electrocardiogram The QT interval QTcF corrected by the Fridericia method islt470 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 advancedmetastatic 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 andor 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 drugtrial 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 medicationtreatment
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None