A Tolerability and Pharmacokinetics Study of SHR6390 in Advanced Melanoma Patients

Hengrui Medicine

Status and phase

Unknown

Phase 1

Conditions

Melanoma

Treatments

Drug: SHR6390

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02671513

SHR6390-I-102

Details and patient eligibility

About

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.

Enrollment

30 estimated patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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