Study of Chiauranib in Patients With Advanced Hepatocellular Carcinoma

NCT03245190 | Completed Phase 1

• 1 other identifier: CAR104
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

Chiauranib, which simultaneously targets against VEGFR/Aurora B/CSF-1R, several key kinases involved in tumor angiogenesis, tumor cell mitosis, and chronic inflammatory microenvironment.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• 16 weeks progression-free rate (16W-PFR)

  Up to a minimum 16 weeks after the last participant's first dose, or progression, or died, whichever came first

Secondary Outcomes (10)

• Rate of Treatment-Related Adverse Events in Study Participants

  Up to a minimum 20 weeks after the last participant's first dose, or progression, or 75% subjects died, whichever came first, assessed up to 24 months

• Time to progression(TTP)

  Approximately 24 months

• Objective response rate (ORR)

  Approximately 24 months

• Disease-control rate (DCR)

  Approximately 24 months

• Duration of response (DOR)

  Approximately 24 months

Other Outcomes (3)

• Median score of immunohistochemical expressed by Aurora B、CSF-1R and Myc protein.

  Assessed up to 24 months

• Screening characteristics of ctDNA measurement (single gene analysis).

  Assessed up to 24 months

• Screening characteristics of ctDNA measurement (multi-gene analysis).

  Assessed up to 24 months

Study Arms (1)

Chiauranib

EXPERIMENTAL

Patients take Chiauranib capsules 50mg, orally once daily, 28 days as a cycle.

Drug: Chiauranib

Interventions

Chiauranib DRUG

50mg, orally once daily

Also known as: CS2164

Chiauranib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age ≥ 18 years and ≤70 years.
• Histological or cytological confirmation of HCC (hepatocellular carcinoma) or non-invasive diagnosis of HCC as per American Association for the Study of Liver Diseases criteria in patients with a confirmed diagnosis of cirrhosis.
• Barcelona Clinic Liver Cancer stage Category B or C that cannot benefit from treatments of locoregional therapy, or provided that progression has been documented after these therapies.
• Patients should have failed or been intolerant of at least one prior systemic therapy regimen which could include systemic chemotherapy (such as oxaliplatin, arsenious acid) and/or sorafenib.
• At least one uni-dimensional measurable lesion according to RECIST (RECIST version 1.1), and modified RECIST for HCC (mRECIST)：a. HCC lesions should have at least one accurate repeated dimension as 1 cm or more ); b. extrahepatic lesions: a lymph node must be 1.5 cm or more in short axis, and Non-lymph node lesions must be at least 1 cm in longest diameter. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, may be considered measurable if there has been demonstrated progression in the lesion.
• Liver function status Child-Pugh Classification with score ≤ 7 points. Child Pugh status should be calculated based on clinical findings and laboratory results during the screening period.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Laboratory criteria are as follows (laboratory results within 7 days prior to first dose, and without receiving any supportive treatment for the following parameters within 2 weeks from the last dose prior to study entry):
• Complete blood count: white blood cell count ≥ 3.0×109/L; absolute neutrophil count (ANC) ≥1.5×109/L ;hemoglobin (Hb) ≥85g/L ; platelets \>=60×109/L
• Biochemistry test: total bilirubin≦1.5×ULN; alanine aminotransferase(ALT) ,aspartate aminotransferase(AST)≦5×ULN ; plasma albumin≥ 28 g/L; serum creatinine(cr)≦1.5×ULN; serum amylase≦1.5×ULN;
• Coagulation test: International Normalized Ratio (INR) \< 1.5; activated partial thromboplastin time (APTT) \< 1.5×ULN
• Thyroid function test: thyroid stimulating hormone (TSH) \< 10mIU/L；
• Life expectancy of at least 12 weeks.
• All patients must have given signed, informed consent prior to registration on study.

You may not qualify if:

• Any target treatment like sorafenib within 2 weeks prior to first dose of study drug; With the exception of target treatment, any anti-cancer systemic treatment (including chemotherapy, immunotherapy, radiotherapy, and anti-cancer Chinese traditional medicine, et al) or locoregional therapy (including but not limited to surgery, radiofrequency ablation or transarterial chemoembolization ) within 4 weeks prior to first dose of study drug; any supportive treatment for haematology (including transfusion, blood products, or drugs that stimulate blood cells growth like G-CSF, et al) within 2 weeks prior to first dose of study drug.
• Known Cholangiocarcinoma or Fibrolamellar Hepatocellular Carcinoma; Known history of, or ongoing second primary cancer, except: adequately treated basal cell or squamous cell skin cancer, curatively treated in-situ cancer of the cervix, unless received curative treatment and with documented evidence of no recurrence during the past five years;
• Known metastatic brain or meningeal tumors
• Patients with uncontrolled or significant cardiovascular disease, including:
• Grade II or higher Congestive heart failure, unstable angina pectoris, myocardial infarction (NYHA Classification) within 6 months prior to study entry; or arrhythmia requiring treatment, or Left Ventricular Ejection Fraction (LVEF) \< 50% during screening stage.
• Primary cardiomyopathy (dilated cardiomyopathy, hypertrophic cardiomyocyte, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, et,al).
• History of significant QT interval prolongation, or Corrected QT Interval QTc≥450ms(male), QTc≥470ms（female）at screening.
• Symptomatic coronary heart disease requiring treatment.
• Uncontrolled hypertension (\> 140/90 mmHg) with single medication.
• History of active bleeding within 6 months or esophageal varices bleeding led by portal hypertension within 2 months prior to screening ; or patients receiving anticoagulation therapy; or patients with evidence of GI bleeding potential.
• Uncontrolled ascites or pleural effusion (defined as not easily controlled with diuretic or paracentesis treatment).
• History of transjugular intrahepatic portosystemic shunts (TIPSS).
• History of abdominal fistula, gastrointestinal perforation or abdominal abscess within 28 days prior to screening.
• History of deep vein thrombosis or pulmonary embolism.
• History of interstitial lung disease(ILD), or with ongoing signs and symptoms at the time of screening.

Sponsors & Collaborators

• Chipscreen Biosciences, Ltd.: lead

Study Sites (1)

Zhongshan Hospital of Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

chiauranib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

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: August 4, 2017
• First Posted: August 10, 2017
• Study Start: April 28, 2018
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2019
• Last Updated: June 18, 2021

Record last verified: 2021-06

Locations

CN (1)