Clinical trial NCT04192903: Chidamide Combined With Cisplatin for Relapsed or Metastatic Triple-negative Breast Cancer
Official title: Chidamide Combined With Cisplatin for Relapsed or Metastatic Triple-negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Triple-negative Breast Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2019-12-10
Enrollment: 55
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to evaluate therapeutic efficacy and safety of Chidamide combined with Cisplatin for relapsed or metastatic triple-negative breast cancer.

Detailed description: Triple-negative breast cancer (TNBC), the most difficult-to-treat breast cancer subtype, lacks well-defined treatment options. This is a prospective, single-center, one-arm, open-label, phase II clinical trial evaluating the efficacy and safety of chidamide in combination with cisplatin in subjects with relapsed or metastatic triple-negative breast cancer.

Eligibility criteria: Inclusion Criteria:

1. Female patients aged 18-75 years (including cutoff value).
2. Patients with recurrent or metastatic breast cancer , histologically proven invasive breast carcinoma with triple negative receptor status (Estrogen receptor, Progesterone receptor and HER2 negative by IHC and FISH) by histopathology in Department of Pathology, Fudan University Cancer Center, Local recurrence needs to be confirmed by the physician that is unresectable.
3. Prior treatment:Previously received no more than 1prior lines of systemic chemotherapy for metastatic breast cancer, and progressed after treatment, chemotherapy regimen did not contain cisplatin or did not demonstrate cisplatin resistance (disease progression during the cisplatin treatment period or within 3 months after completion);
4. At least one extracranial measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.
5. Eastern Cooperative Oncology Group Performance Status of 0-1.
6. Life expectancy ≥ 3 months.
7. Adequate function of major organs meets the following requirements (no blood components and cell growth factors have been used within 14 days before randomization):

   Neutrophils ≥ 1.5×10\^9/L Platelets ≥ 90×10\^9/L Hemoglobin ≥ 90g/L Total bilirubin≤ 1.5 × the upper limit of normal (ULN) ALT and AST ≤ 2.5 × ULN BUN and Cr ≤ 1.5 × ULN Left ventricular ejection fraction (LVEF) ≥ 50% QTcF(Fridericia correction) ≤ 470 ms International normalized ratio(INR)≤1.5 × ULN，activated partial thromboplastin time(APTT) ≤ 1.5 × ULN
8. Subjects voluntarily joined the study, signed informed consent.

Exclusion Criteria:

1. Previously received any HDAC inhibitor treatment.
2. The subject has untreated central nervous system (CNS) metastases.
3. Patients who have undergone systemic, radical brain or meningeal metastasis (radiotherapy or surgery), but have been confirmed to have been stable for at least 4 weeks, and who have stopped systemic hormonal therapy for more than 2 weeks without clinical symptoms can be included.
4. Previously received more than 2 lines of systemic chemotherapy for metastatic breast cancer.
5. There are ascites, pleural effusion, pericardial effusion with clinical symptoms at baseline, those who need drainage, or those who have undergone drainage of serous effusion within 4 weeks before the first dose.
6. Inability to swallow, intestinal obstruction or other factors affecting the administration and absorption of the drug.
7. Received systemic therapy such as chemotherapy, molecular targeted therapy or other clinical trial drugs within 4 weeks before enrollment;
8. Patients with other malignant tumors within 5 years or at the same time( except for cured skin basal cell carcinoma and cervical carcinoma in situ).
9. Have undergone major surgical procedures or significant trauma within 4 weeks prior to randomization, or are expected to undergo major surgery.
10. Have a history of allergies to the drug components of this regimen.
11. Patients with active HBV and HCV infection; stable hepatitis B after drug treatment (HBV virus copy number is higher than the upper limit of reference value) and cured hepatitis C patients (HCV virus copy number exceeds the lower limit of detection method) can be included.
12. History of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency disease, history of organ transplantation.
13. History of cardiac dysfunction, include(1)angina (2)clinical significant arrythmia or require drug intervention (3)myocardial infarction (4)heart failure (5) other cardiac dysfunction (judged by the physician); any cardiac or nephric abnormal ≥ grade 2 found in screening.
14. Female patients who are pregnancy, lactation or women who are of childbearing potential tested positive in baseline pregnancy test. Childbearing female who refuse to accept any contraception practice during the treatment period and for at least 8 weeks after the last dose of chemotherapy.
15. Determined by the physician, any serious coexisting disease might be harmful to the patient's safety or avoid the patients from accomplishing the treatment(e.g serious hypertension, diabetes, thyroid dysfunction, active infection etc.).
16. History of neurological or psychiatric disorders, including epilepsy or dementia.
17. The investigator determined who was not suitable for the study.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: From the day of treatment to the date of first documented progression，up to 18 months after the last patient's enrollment
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: From the day of treatment to the date of first documented progression，up to 18 months after the last patient's enrollment
measure: Overall survival (OS)
timeFrame: From the day of treatment to the date of first documented progression，up to 18 months after the last patient's enrollment
measure: Duration of remission (DOR)
timeFrame: From the day of treatment to the date of first documented progression，up to 18 months after the last patient's enrollment
measure: Clinical Benefit Rate (CBR)
timeFrame: From the day of treatment to the date of first documented progression，up to 18 months after the last patient's enrollment
measure: Adverse event(AE)
timeFrame: From the day of treatment to the date of first documented progression，up to 18 months after the last patient's enrollment
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
Study officials:
affiliation: Fudan University
name: xichun Hu,MD
role: STUDY_DIRECTOR
affiliation: Fudan University
name: Jian Zhang,MD
role: PRINCIPAL_INVESTIGATOR
References: