Neoplasm
Conditions
Keywords
neoplasm, Cycline-Dependent Kinase
Brief summary
SHR6390 is a small molecular, oral potent, selective CDK4/6 inhibitor. The purpose of this study is to investigate the safety/tolerability and the pharmacokinetic profile of SHR6390 in Chinese advanced solid tumor patients by using a 3+3 dose escalation.Preliminary efficacy will be also investigated in this study.
Interventions
DRUGSHR6390
SHR6390 either 25, 50mg, 75mg, 100mg, 125mg, 150mg, 175mg given orally, QD
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Pathologically confirmed solid tumor and failed from all standard treatment * Eastern Cooperative Oncology Group (ECOG) performance status: 0-1 * Life expectancy ≥ 3 months * Adequate function of major organs, meaning the following criteria should be met within 14 days before randomization: * Hemoglobin \> 110g/L * Neutrophils \> 2.0×10\^9/L * Platelets \> 100×10\^9/L * Total bilirubin \< 1.5×the upper limit of normal (ULN) * ALT and AST ≤ 1.5×ULN (≤ 5×ULN, if existing liver metastases) * Creatinine ≤ 1 ULN * Left ventricular ejection fraction (LVEF) ≥ 50% * QTcF(Fridericia correction) male≤450 ms, female≤470 ms * Good compliance of patient by physician's judgement * Signed and dated informed consent
Exclusion criteria
* Previously received therapy of anti-tumor agent targeting at CDK4/6 * Less than 3 weeks from the last cell-toxicity chemotherapy, less than 6 weeks from last mitomycin or nitrosamine therapy * Less than 3 weeks from any other anti-tumor therapy (including targets therapy, immunotherapy or other approved therapy) * Having joined in other clinical trials within 4 weeks * Uncontrolled/untreated brain metastasis (well-controlled/well-treated brain metastasis by physician's judgement is allowed) * existing abnormal CTCAE≥grade 2 resulted from previous treatment(except grade 2 alopecia) * uncontrollable symptomatic pleural effusion or ascites or require clinical intervention * require continous treatment by steroids * Factors influencing the usage of oral administration (e.g. unable to swallow, chronic diarrhea and intestinal obstruction, etc.) * existing uncontrollable hypokalemia or hypomagnesemia * history of serious allergy events or known being allergy constitution * active HBV or HCV infection (HBV virus≥10e4 copies/ml, HCV virus≥10e3 copies/ml) * History of immunodeficiency, acquired or congenital immunodeficiency, history of organ transplantation * 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 * 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 * determined by the physician, any coexisting disease might lead to life threatening complications or avoid the patients from accomplishing the treatment(e.g serious hypertension, diabetes, thyroid dysfunction,etc.) * history of neuropathy or dysphrenia, including epilepsy and dementia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose | 5 weeks | The maximum-tolerated dose (MTD) will be defined as the maximum dose level at which no more than one out of three subjects experience a dose-limiting toxicity (DLT) within the first 3 week of the first cycle of multiple dosing |
Secondary
| Measure | Time frame |
|---|---|
| Evaluation of pharmacokinetic parameter of SHR6390: Cmax | 6 weeks |
| Evaluation of pharmacokinetic parameter of SHR6390: Tmax | 6 weeks |
| Number of patients experience adverse events | up to 12 months |
| Evaluation of pharmacokinetic parameter of SHR6390: AUC | 6 weeks |
| Objective Response Rate | every 8 weeks, up to 12 months |
| Evaluation of pharmacokinetic parameter of SHR6390: t1/2 | 6 weeks |
Countries
China
Outcome results
None listed