Patient case: 70-year-old male with melanoma; genetic feature: NF1 truncation

Clinical trial: A Tolerability and Pharmacokinetics Study of SHR6390 in Advanced Melanoma Patients

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.


Eligibility: 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

Relevance to patient case: not relevant