A Tolerability and Pharmacokinetics Study of SHR6390 in Advanced Melanoma Patients

• Status: Unknown status
• Trial end date: 2017-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Collaborator: Beijing Cancer Hospital

Criteria

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