A Study of SHR6390 in Advanced Solid Tumor Patients

A Tolerability and Pharmacokinetics Study of SHR6390 in Advanced Solid Tumor 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 solid tumor patients by using a "3+3" dose escalation.Preliminary efficacy will be also investigated in this study.

Study Overview

• Status: Completed
• Conditions: Neoplasm
• Intervention / Treatment: Drug: SHR6390

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Cancer hospital, Chinese Academy of Medical Sciences

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 solid tumor and failed from all standard treatment
• 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 > 110g/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(except grade 2 alopecia)
• 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 25, 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	5 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	up to 12 months
Objective Response Rate	every 8 weeks, up to 12 months

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Binhe Xu, M.D, Cancer Hosptial, Chinese Academy of Medical Sciences

Publications and helpful links

General Publications

• Zhang P, Xu B, Gui L, Wang W, Xiu M, Zhang X, Sun G, Zhu X, Zou J. A phase 1 study of dalpiciclib, a cyclin-dependent kinase 4/6 inhibitor in Chinese patients with advanced breast cancer. Biomark Res. 2021 Apr 12;9(1):24. doi: 10.1186/s40364-021-00271-2.

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2016
• Primary Completion (Actual): June 28, 2019
• Study Completion (Actual): June 28, 2019

Study Registration Dates

• First Submitted: February 12, 2016
• First Submitted That Met QC Criteria: February 16, 2016
• First Posted (Estimate): February 17, 2016

Study Record Updates

• Last Update Posted (Actual): July 11, 2022
• Last Update Submitted That Met QC Criteria: July 7, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: neoplasm, Cycline-Dependent Kinase
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SHR6390-I-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED