A Tolerability and Pharmacokinetics Study of SHR6390 in Advanced Melanoma Patients

Melanoma Clinical Trial

Official title:

A Tolerability and Pharmacokinetics Phase 1 Study of SHR6390 in Advanced Melanoma Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02671513
• Other study ID #: SHR6390-I-102
• Status: Recruiting
• Phase: Phase 1
• First received: January 24, 2016
• Last updated: April 11, 2016
• Start date: January 2016
• Est. completion date: April 2017

Study information

• Verified date: January 2016
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: Jun Guo, M.D
• Email: guoj307[@]126.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: April 2017
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• SHR6390
SHR6390 either 50mg,75mg,100mg,125mg,150mg,175mg given orally, QD

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing

Sponsors (2)

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

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose	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.	3 weeks	Yes
Secondary	Evaluation of pharmacokinetic parameter of SHR6390: Cmax		6 weeks	No
Secondary	Evaluation of pharmacokinetic parameter of SHR6390: Tmax		6 weeks	No
Secondary	Evaluation of pharmacokinetic parameter of SHR6390: t1/2		6 weeks	No
Secondary	Evaluation of pharmacokinetic parameter of SHR6390: AUC		6 weeks	No
Secondary	Number of patients experience adverse events		6 months	Yes
Secondary	objective response rate		every 8 weeks, up to 12 months	No