A Tolerability and Pharmacokinetics Study of SHR6390 in Advanced Melanoma Patients

NCT02671513 | Unknown Phase 1

• 1 other identifier: SHR6390-I-102
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Melanoma

Keywords

Melanoma; Cycline-Dependent Kinase

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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

Study Arms (1)

SHR6390

EXPERIMENTAL

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

Drug: SHR6390

Interventions

SHR6390 DRUG

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

SHR6390

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead
• Peking University Cancer Hospital & Institute: collaborator

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

RECRUITING

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Jun Guo, M.D

  Beijing Cancer hospital,Peking University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Guo, M.D

CONTACT

guoj307@126.com

Yi Liu, Ph.D

CONTACT

liuy@shhrp.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2016
• First Posted: February 2, 2016
• Study Start: January 1, 2016
• Primary Completion: November 1, 2016
• Study Completion: April 1, 2017
• Last Updated: April 12, 2016

Record last verified: 2016-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)