Hepatocellular CarcinomaPhase 1/2NCT03245190
Study of Chiauranib in Patients With Advanced Hepatocellular Carcinoma
A Phase 1/2 study testing Chiauranib in people with Hepatocellular Carcinoma, run by Chipscreen Biosciences, Ltd. at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Chiauranib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteChina
- Study dates
- 28 Apr 2018to 1 Nov 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 14Show fewer
- 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.
Who cannot join
- 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).
Show all 29Show fewer
- 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.
- History of hypothyroidism; or patients receiving substitutional treatment with thyroid hormone.
- With any ongoing toxicities (>CTCAE grade 1) caused by previous cancer therapy.
- Patients with factors that could affect oral medication (such as dysphagia, chronic diarrhea, intestinal obstruction etc), or undergone gastrectomy.
- History of liver transplantation, or patients in preparation of liver transplantation.
- 6 weeks or less from the last major surgery that involved general anaesthesia, or 2 weeks or less from the last minor surgery prior to screening (excluding placement of vascular access ) .
- Proteinuria positive(≥1g/24h).
- Patients with active or unable to control infections including human immunodeficiency virus (HIV), or other serious infectious diseases.
- Patients with untreated active hepatitis B virus (HBV) (HBsAg positive and HBV DNA ≥ 2000 IU/mL) . But patients with controlled(treated) HBV fulfilling the following criteria can be eligible for the study: HBV DNA< 2000 IU/mL , or patients on anti-HBV suppression with HBV DNA< 2000 IU/mL before study enrollment.
- Patients with untreated active hepatitis C virus.
- Any mental or cognitive disorder, that would impair the ability to understand the informed consent document, or limit compliance with study requirements/treatment.
- Any previous treatment with aurora kinase inhibitors.
- Candidates with drug abuse.
- Women of childbearing potential not willing to use and utilize an adequate method of contraception (such as intrauterine device, contraceptive and condom) throughout treatment and for at least 12 weeks after the last dose; pregnant or breastfeeding women; the result of urine pregnancy test was positive at screening; Man participants not willing to use and utilize an adequate method of contraception throughout treatment.
- Any other condition which is inappropriate for the study according to investigators' judgment.
Trial locations and contacts
1 site in 1 country.
China1 site
Zhongshan Hospital of Fudan University
Shanghai, Shanghai Municipality, 200032
About this study
Official title: Efficacy and Safety of Chiauranib in Advanced Hepatocellular Carcinoma: a Single-arm, Open-label, Multi-center, Exploratory Phase Ib Study
Chiauranib, which simultaneously targets against VEGFR/Aurora B/CSF-1R, several key kinases involved in tumor angiogenesis, tumor cell mitosis, and chronic inflammatory microenvironment.
Read the detailed description
Chiauranib is a novel orally active multi-target inhibitor that simultaneously inhibits the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRa and c-Kit), mitosis-related kinase Aurora B and chronic inflammation related kinase CSF-1R in a high potency manner with the IC50 at a single-digit nanomolar range. In particular, Chiauranib showed very high selectivity in the kinase inhibition profile with little activity on off-target non-receptor kinases, proteins, GPCR and ion channels, indicative of a better drug safety profile in terms of clinical relevance.
Because of its broad preclinical anti-tumor efficacy and the potential to improve conventional TKI kinase inhibitor therapy in various cancer indications, Chiauranib has now entered phase Ib clinical trials.
This clinical trial is studying the efficacy and safety of chiauranib works in treating patients with advanced hepatocellular carcinoma, in the meantime, exploring the latent biomarkers accompany with chiauranib, as well as the relevancy of which and clinical benefit.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Chiauranib
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChiauranibDrug
Also called CS2164
50mg, orally once daily
| Study group | Role | What they receive |
|---|---|---|
| Chiauranib | Experimental | Patients take Chiauranib capsules 50mg, orally once daily, 28 days as a cycle. Receives: Drug: Chiauranib |
What is being measured
The primary outcome is the main question the study is designed to answer.
16 weeks progression-free rate (16W-PFR)
Measured: 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
Safety evaluation as measured by adverse events (AE), vital signs，electrocardiograph(ECG) and abnormal laboratory results according to CTCAE V4.03
Measured: 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)
Measured: Approximately 24 months
Objective response rate (ORR)
ORR is defined as the percentage of participants whose best overall response is either complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and modified RECIST for HCC (mRECIST), respectively.
Measured: Approximately 24 months
Disease-control rate (DCR)
Measured: Approximately 24 months
Duration of response (DOR)
Measured: Approximately 24 months
Progression-free survival (PFS)
Measured: Approximately 24 months
Overall survival (OS)
Measured: Approximately 24 months
6 months progression-free rate
Measured: At 6 months
6 months overall survival rate
Measured: At 6 months
12 months overall survival rate
Measured: At 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2017
- Study start28 Apr 2018
- Primary completion1 Nov 2019
- Study completion1 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Chipscreen Biosciences, Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chipscreen Biosciences, Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03245190
- Sponsor's protocol ID
- CAR104
- Status last verified
- Jun 2021
- First submitted
- 4 Aug 2017
- Last updated
- 18 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Chiauranib in Advanced Hepatocellular Carcinoma: a Single-arm, Open-label, Multi-center, Exploratory Phase Ib Study
- ClinicalTrials.gov ID
- NCT03245190
- Acronym / sponsor ID
- CAR104
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Chipscreen Biosciences, Ltd.Industry (pharma, biotech, devices)
- Study start
- 28 Apr 2018 (actual)
- Primary completion
- 1 Nov 2019 (actual)
- Study completion
- 1 Nov 2019 (actual)
- First posted
- 10 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chiauranib, which simultaneously targets against VEGFR/Aurora B/CSF-1R, several key kinases involved in tumor angiogenesis, tumor cell mitosis, and chronic inflammatory microenvironment.
Detailed description
Chiauranib is a novel orally active multi-target inhibitor that simultaneously inhibits the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRa and c-Kit), mitosis-related kinase Aurora B and chronic inflammation related kinase CSF-1R in a high potency manner with the IC50 at a single-digit nanomolar range. In particular, Chiauranib showed very high selectivity in the kinase inhibition profile with little activity on off-target non-receptor kinases, proteins, GPCR and ion channels, indicative of a better drug safety profile in terms of clinical relevance.
Because of its broad preclinical anti-tumor efficacy and the potential to improve conventional TKI kinase inhibitor therapy in various cancer indications, Chiauranib has now entered phase Ib clinical trials.
This clinical trial is studying the efficacy and safety of chiauranib works in treating patients with advanced hepatocellular carcinoma, in the meantime, exploring the latent biomarkers accompany with chiauranib, as well as the relevancy of which and clinical benefit.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chiauranib | Experimental | Drug: ChiauranibPatients take Chiauranib capsules 50mg, orally once daily, 28 days as a cycle. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (29 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ChiauranibAlso: CS216450mg, orally once daily | Drug | Chiauranib |
Primary outcome
16 weeks progression-free rate (16W-PFR)
Time frame: Up to a minimum 16 weeks after the last participant's first dose, or progression, or died, whichever came first
10 secondary outcomes
Rate of Treatment-Related Adverse Events in Study Participants
Time frame: 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)
Time frame: Approximately 24 months
Objective response rate (ORR)
Time frame: Approximately 24 months
Disease-control rate (DCR)
Time frame: Approximately 24 months
Duration of response (DOR)
Time frame: Approximately 24 months
Progression-free survival (PFS)
Time frame: Approximately 24 months
Overall survival (OS)
Time frame: Approximately 24 months
6 months progression-free rate
Time frame: At 6 months
6 months overall survival rate
Time frame: At 6 months
12 months overall survival rate
Time frame: At 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2021.
- Individual participant dataSharing planned: Undecided
Related trials for Hepatocellular Carcinoma
RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingObservational study
A Study to Evaluate Patient-Reported Satisfaction, Effectiveness, and Safety of Atezolizumab in Participants Treated in Routine Clinical Practice
Lung Cancer, Hepatocellular Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Chiauranib in people with Hepatocellular Carcinoma, run by Chipscreen Biosciences, Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
16 weeks progression-free rate (16W-PFR) (time frame: Up to a minimum 16 weeks after the last participant's first dose, or progression, or died, whichever came first). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2021.