Clinical trial NCT02671513: A Tolerability and Pharmacokinetics Study of SHR6390 in Advanced Melanoma Patients
Official title: A Tolerability and Pharmacokinetics Phase 1 Study of SHR6390 in Advanced Melanoma Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Melanoma
Keywords: Melanoma
Cycline-Dependent Kinase
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Peking University Cancer Hospital & Institute
First posted: 2016-02-02
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Maximum Tolerated Dose
timeFrame: 3 weeks
Secondary outcomes:
measure: Evaluation of pharmacokinetic parameter of SHR6390: Cmax
timeFrame: 6 weeks
measure: Evaluation of pharmacokinetic parameter of SHR6390: Tmax
timeFrame: 6 weeks
measure: Evaluation of pharmacokinetic parameter of SHR6390: t1/2
timeFrame: 6 weeks
measure: Evaluation of pharmacokinetic parameter of SHR6390: AUC
timeFrame: 6 weeks
measure: Number of patients experience adverse events
timeFrame: 6 months
measure: objective response rate
timeFrame: every 8 weeks, up to 12 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
affiliation: Beijing Cancer hospital,Peking University
name: Jun Guo, M.D
role: PRINCIPAL_INVESTIGATOR
References: