A Tolerability and Pharmacokinetics Study of SHR6390 in Advanced Melanoma Patients

Phase 1

• Conditions: Melanoma
• Interventions: Drug: SHR6390

• Registration Number: NCT02671513
• Lead Sponsor: Jiangsu HengRui Medicine Co., Ltd.

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2016-01
• Study Start: 2016-01
• Study First Submitted: 2016-01-24
• Study First Submitted QC: 2016-02-01
• Study First Posted: 2016-02-02
• Last Update Submitted: 2016-04-11
• Last Update Posted: 2016-04-12
• Primary Completion: 2016-11
• Study Completion: 2017-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SHR6390	SHR6390	Each subject will receive a single dose of SHR6390 and then repeat doses following a 3 week/1 week off regimen.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Evaluation of pharmacokinetic parameter of SHR6390: Cmax	6 weeks
Evaluation of pharmacokinetic parameter of SHR6390: Tmax	6 weeks
Evaluation of pharmacokinetic parameter of SHR6390: t1/2	6 weeks
Evaluation of pharmacokinetic parameter of SHR6390: AUC	6 weeks
Number of patients experience adverse events	6 months
objective response rate	every 8 weeks, up to 12 months

Trial Locations

Locations (1)

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, China