Melanoma
Conditions
Keywords
Melanoma, 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 melanoma patients by using a 3+3 dose escalation.Preliminary efficacy will be also investigated in this study.
Interventions
DRUGSHR6390
SHR6390 either 50mg,75mg,100mg,125mg,150mg,175mg given orally, QD
Sponsors
Peking University Cancer Hospital & Institute
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 melanoma * Unresectable stage III or IV melanoma patient * companion with cell cycle pathway abnormal (e.g CDK4 amplify and/or CCND1 amplify and/or CDKN2A loss) * 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 \> 100g/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 * 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 | 3 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: AUC | 6 weeks |
| Number of patients experience adverse events | 6 months |
| Evaluation of pharmacokinetic parameter of SHR6390: t1/2 | 6 weeks |
| Evaluation of pharmacokinetic parameter of SHR6390: Cmax | 6 weeks |
| Evaluation of pharmacokinetic parameter of SHR6390: Tmax | 6 weeks |
| objective response rate | every 8 weeks, up to 12 months |
Countries
China
Contacts
Primary ContactJun Guo, M.D
Backup ContactYi Liu, Ph.D
Outcome results
None listed