Trial Title:
Chidamide/Everolimus for PIK3CA Wild-type/Mutant HR+/HER2- Advanced Breast Cancer
NCT ID:
NCT05983107
Condition:
HR+/HER2- Advanced Breast Cancer
Targeted Therapy
Conditions: Official terms:
Breast Neoplasms
Everolimus
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Everolimus
Description:
Everolimus combined with endocrine therapy（tamoxifen, letrozole, anastrozole, exemestane,
fulvestrant, etc.Goserelin, leuprolide, premenopausal patients only, selected at the
discretion of the investigator）
Arm group label:
cohort 1 PIK3CA Mutant
Intervention type:
Drug
Intervention name:
Chidamide
Description:
Chidamide combined with endocrine therapy（tamoxifen, letrozole, anastrozole, exemestane,
fulvestrant, etc.goserelin, leuprolide, premenopausal patients only, selected at the
discretion of the investigator）
Arm group label:
cohort 2 PIK3CA wild type
Intervention type:
Drug
Intervention name:
Endocrine therapy
Description:
Tamoxifen, letrozole, anastrozole, exemestane, fulvestrant, etc, selected at the
discretion of the investigator.
Arm group label:
cohort 1 PIK3CA Mutant
Arm group label:
cohort 2 PIK3CA wild type
Intervention type:
Drug
Intervention name:
Ovarian function suppression(OFS)
Description:
Goserelin, leuprolide, premenopausal patients only, selected at the discretion of the
investigator.
Arm group label:
cohort 1 PIK3CA Mutant
Arm group label:
cohort 2 PIK3CA wild type
Summary:
To explore the efficacy and safety of chidamide combined with endocrine in
phosphoinositide-3-kinase,catalytic,alpha gene(PI3KCA) wild type hormone receptor
positive(HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced breast
cancer patients and to explore the efficacy and safety of Everolimus combined with
endocrine therapy in patients with PI3KCA Mutant HR+/HER2- advanced breast cancer.
Detailed description:
This study is an open, multi center, prospective cohort, and Phase II exploratory
research. According to the PIK3CA gene mutation status of patients, the study is divided
into two cohorts. The PIK3CA Mutant uses everolimus combined with endocrine therapy as
the cohort A, and the PIK3CA wild type uses chidamide combined with endocrine therapy as
the cohort B, until the disease progresses or the toxicity is intolerable. According to
the judgment of the researchers, whether to enter the second stage of cross design, Queue
A was cross administered with chidamide in combination with endocrine therapy. Cohort B
cross used everolimus combined with endocrine until the disease progressed or the
toxicity was intolerable.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- The age at the time of signing the informed consent form is ≥ 18 years old and ≤ 75
years old, for menopausal/premenopausal women (premenopausal women need to receive
ovarian function suppression treatment at the same time).
- Breast cancer patients with HR positive (ER expression ≥ 10%, PR positive or
negative) and HER2 negative (Immunohistochemical(IHC)0,1+; 2+, Fluorescence in situ
hybridization(FISH) not expanded) confirmed by histology.
- Histologically confirmed locally advanced breast cancer (no radical local treatment)
or recurrent and metastatic breast cancer.
- The patients who had previously progressed after the treatment of first-line or
second-line cyclin-dependent kinases 4 and 6 inhibitors（CDK4/6 inhibitors）of
endocrine and whose chemotherapy was ≤ second-line (relapse during the period of new
adjuvant/adjuvant treatment or within 12 months after the end of treatment was
regarded as first-line chemotherapy), the PIK3CA gene mutation detection was
performed a. PIK3CA Mutant subjects were enrolled in queue A; b. PIK3CA wild-type
subjects were included in queue B.
- At least one measurable primary lesion (according to RECIST v1.1 standard) before
enrollment.
- The Eastern Oncology Collaborative Group (ECOG) physical fitness score is 0-2.
- The toxic and side effects caused by previous anti-tumor therapy were relieved to
0-1 levels before the screening period (judged according to The NCI Common
Terminology Criteria for Adverse Events version5.0 (NCICTCAE5.0); except for
toxicity that researchers believe does not pose a safety risk to the subjects due to
hair loss).
- The functional level of organs must meet the following requirements: 1) Blood
routine:
Absolute neutrophil count(ANC)≥1.5 × 109/L (growth factor not used within 14 days);
Platelet(PLT) ≥100 × 109/L (no corrective treatment used within 7 days); Hb ≥ 100 g/L
(without corrective treatment within 7 days); 2) Blood biochemistry: Total
bilirubin(TBIL) ≤1.5 × upper limits of normal(ULN); Glutamine
aminotransferase(ALT),Glutamic transaminase(AST)≤3 × ULN; Glutamine transpeptidase(GGT)
≤2.5 × ULN; If there is liver metastasis, then ALT and/or AST ≤ 5 × ULN; Glutamine
transpeptidase GGT ≤5 × ULN; Urea, Blood urea nitrogen (BUN), creatinine (Cr) ≤1.5 × ULN;
3) Cardiac ultrasound: Left ventricular ejection fraction（LVEF）≥ 50%; 4) 12 lead ECG: QT
interval (QTcF) corrected by Fridericia method, male<450ms, female.
- Expected survival time ≥ 3 months.
- Voluntarily participate in this clinical trial and sign a written informed consent
form.
Exclusion Criteria:
- Those who have received any mammalian target of rapamycin（mTOR） and histone
deacetylase（HDAC） inhibitors at any time in the past.
- Received chemotherapy, Targeted therapy, immunotherapy, interventional therapy or
other systematic anti-tumor treatment within 4 weeks before the first administration
of the study drug, or received radiotherapy within 3 weeks Note: Nitroso urea or
Mitomycin C is within 6 weeks before the first use of the study drug, oral
fluorouracil and small molecule targeted drugs are within 2 weeks before the first
use of the study drug or within 5 half lives of the drug (whichever is longer),
Traditional Chinese medicine with anti-tumor indications should be used within 2
weeks before the first use of the study drug.
- Subjects who have undergone major surgical procedures or obvious trauma within 4
weeks prior to enrollment, or are expected to undergo major surgical treatment.
- Subjects with brain or subdural metastasis are excluded. Unless its stability has
been maintained for at least 4 weeks or Asymptomatic brain metastasis can be
included in the group.
- According to the investigator's judgment, there are concomitant diseases (such as
severe hypertension, Thyroid disease, hyperlipidemia, active infection, etc.) that
seriously endanger the patient's safety or affect the patient's completion of the
study.
- Patients with poor control of diabetes shall be determined by the researcher.
- Clinically obvious gastrointestinal abnormalities that may affect drug intake,
transport or absorption (such as inability to swallow, chronic diarrhea, Bowel
obstruction, etc.).
- Severe cardiovascular injury (greater than a history of congestive heart failure at
New York Heart Association(NYHA) level II, unstable angina or myocardial infarction
within the past 6 months, or severe arrhythmia.
- Subjects have active hepatitis (hepatitis B reference: HBsAg positive and hepatitis
B virus(HBV) DNA ≥ 500 international unit(IU)/ml; hepatitis C reference: hepatitis C
virus(HCV) antibody positive and HCV copy number>upper limit of normal value);
Subjects who are known to be positive for human immunodeficiency virus (HIV).
- Female patients during pregnancy and lactation, female patients with Fertility and
positive baseline Pregnancy test, or those of childbearing age who are unwilling to
take effective contraceptive measures during the whole test period and within 90
days after the last administration of the study drug.
- Have a clear history of neurological or mental disorders, including epilepsy or
dementia, in the past.
- Any medical condition in which the researcher believes that the subject is not
suitable for entry into the study.
Gender:
Female
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Address:
City:
Beijing
Zip:
100021
Country:
China
Status:
Recruiting
Contact:
Last name:
Fei Ma
Phone:
010-87788120
Email:
drmafei@126.com
Start date:
July 20, 2023
Completion date:
July 15, 2027
Lead sponsor:
Agency:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Agency class:
Other
Source:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05983107
