A Tolerability and Pharmacokinetics Study of SHR6390 in Advanced Melanoma Patients

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

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.

Study Overview

• Status: Unknown
• Conditions: Melanoma
• Intervention / Treatment: Drug: SHR6390

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Jun Guo, M.D; Email: guoj307@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR6390; Each subject will receive a single dose of SHR6390 and then repeat doses following a 3 week/1 week off regimen.	Drug: SHR6390; SHR6390 either 50mg,75mg,100mg,125mg,150mg,175mg given orally, QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Collaborators: Peking University Cancer Hospital & Institute
• Investigators: Principal Investigator: Jun Guo, M.D, Beijing Cancer hospital,Peking University

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): November 1, 2016
• Study Completion (Anticipated): April 1, 2017

Study Registration Dates

• First Submitted: January 24, 2016
• First Submitted That Met QC Criteria: February 1, 2016
• First Posted (Estimate): February 2, 2016

Study Record Updates

• Last Update Posted (Estimate): April 12, 2016
• Last Update Submitted That Met QC Criteria: April 11, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Melanoma; Cycline-Dependent Kinase
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: SHR6390-I-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO