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A Phase II Study of Chiauranib in Combine With Capecitabine in TNBC

Primary Purpose

Triple-negative Breast Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Chiauranib
capecitabine
Sponsored by
Chipscreen Biosciences, Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Triple-negative Breast Cancer focused on measuring Chiauranib;Capecitabine;triple-negative breast cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. All patients must have given signed, informed consent prior to registration on study
  2. age ≥ 18 years
  3. female
  4. Histological or cytological evidence of estrogen-receptor negative (ER-), progesterone receptor negative (PgR-) and human epidermal growth factor-2 receptor negative (HER2-) Breast Cancer by local laboratory testing.
  5. Patients with locally advanced inoperable or recurrent/metastatic TNBC and had failed treatment with anthracyclines and taxanes.
  6. At least 1 lesion can be accurately measured, as defined by RECIST1.1
  7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  8. Laboratory criteria are as follows:

1) Complete blood count: hemoglobin (Hb) ≥90g/L ; absolute neutrophil count (ANC) ≥1.5×109/L ; platelets ≥90×109/L; 2) Biochemistry test: serum creatinine(cr) <1.5×ULN; total bilirubin<1.5×ULN; alanine aminotransferase(ALT) ,aspartateaminotransferase(AST)≤2.5×ULN; (ALT,AST#5×ULN if liver involved) 3) Coagulation test: International Normalized Ratio (INR) < 1.5

9. Life expectancy of at least 3 months

Exclusion Criteria:

  1. Patients have used any anti-cancer therapy, including adiotherapy, chemotherapy, immunotherapy, target therapy, and other anti-tumor treatments within 28 days before the first dose
  2. Patients received vascular endothelial growth factor(VEGF)/vascular endothelial growth factor receptor(VEGFR) inhibitor, like Apatinib, Anlotinib, Fruquintinib, Bevacizumab, etc., or Aurora kinase inhibitors, etc; Patients had treatment of capecitabine (except who received the treatment of capecitabine in Neoadjuvant/ Adjuvant therapy, and Recurrence occurs after 12 months)
  3. Has known allegies to Chiauranib, capecitabine or any of the excipients
  4. prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer
  5. Treatment with an investigational agent/instrument within 28 days prior to first dose of study drug
  6. Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1
  7. Patients with prior invasive malignancies in the past five years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ
  8. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis
  9. Have uncontrolled or significant cardiovascular disease, including:

1) Congestive heart failure, unstable angina pectoris, myocardial infarction within 6 months prior to study entry; arrhythmia, or Left Ventricular Ejection Fraction (LVEF) < 50% requiring treatment with agents during screening stage 2) primary cardiomyopathy(dilated cardiomyopathy, hypertrophic cardiomyocyte, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, et,al) 3) History of significant QT interval prolongation, or Corrected QT Interval (QTc) > 470 ms prior to study entry 4) Symptomatic coronary heart disease requiring treatment with agents 5) History of hypertension treated by≥2 agents, or the Blood pressure(Bp) ≥140/90 mmHg prior to study entry 6) Other condition investigator considered inappropriate

10. CT or MRI of the chest during the screening period shows interstitial lung disease or pulmonary fibrosis or lung inflammation that requires treatment, or within 6 months before the first dose, history of pneumonia requiring oral or intravenous steroid treatment

11. Have clinical significant gastrointestinal abnormality that would impair the ingestion, transportation or absorption of oral agents, history of gastrointestinal perforation or abdominal fistula, peptic ulcer disease within 6 months prior to first dose of study drug

12. Urinary protein ≥ 2+ and quantitative urinary protein ≥ 1g/24 h during the screening period

13. History of active bleeding within the past 2 months, patients with bleeding potential during the screening period, or receiving anticoagulation therapy

14. Pleural fluid, ascites or pericardial effusion with significant symptoms or required treatment of puncture or drainage during the screening period

15. History of deep venous thrombosis or Pulmonary embolism within the past 6 months

16. Active infection requiring oral or intravenous systemic antimicrobial therapy during the screening period

17. Screening for HIV antibody positive

18. Screening test for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive with virus replication, hepatitis C antibody (HCVAb) positive with virus replication

19. Any mental or cognitive disorder, that would impair the ability to understand the informed consent document, or the compliance of study

20. Candidates with drug and alcohol abuse

21. Participants of reproductive potential not willing to use adequate contraceptive measures for the duration of the study.Pregnant or breastfeeding women

22. Any other condition which is inappropriate for the study in the opinion of the investigators

Sites / Locations

  • Sun Yat-sen University Cancer Center
  • Henan Cancer Hospital
  • Jiangsu Province Hospital
  • The Fifth Medical Center of PLA General HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental: Chiauranib + capecitabine

Arm Description

Patients receive the combined treatment of Chiauranib plus capecitabine, 21 days as a cycle until objective disease progression.

Outcomes

Primary Outcome Measures

ORR(Objective reponse rate)
Overall response rate (ORR) is defined as the percentage of patients with complete or partial response evaluated by RECIST 1.1. Per RECIST 1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Secondary Outcome Measures

CBR (Clinical Benefit Rate)
Clinical Benefit Rate (CBR) will be determined by looking at the number of subjects who have either a complete response, partial response, or stable disease for greater than or equal to 24 weeks, per RECIST 1.1
PFS (Progression-free survival)
From date of the first dose of study drug until the date of first documented progression or relapse or date of death from any cause, whichever came first,
DoR (Duration of response)
OS(Overall survival)
AEs
percentage of AEs

Full Information

First Posted
April 14, 2022
Last Updated
April 14, 2022
Sponsor
Chipscreen Biosciences, Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05336721
Brief Title
A Phase II Study of Chiauranib in Combine With Capecitabine in TNBC
Official Title
An Open Labelled, Multicenter-phase II Study of Chiauranib Combine With Capecitabine in Advanced Triple-negative Breast Cancer Failed to Prior Anthracyclines and Taxanes Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 5, 2021 (Actual)
Primary Completion Date
March 15, 2024 (Anticipated)
Study Completion Date
August 9, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chipscreen Biosciences, Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is to evaluate the preliminary efficacy and safety of chiauranib in combine with capecitabine in advanced triple-negative breast cancer failed to prior anthracyclines and taxanes therapy
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 inflammationrelated 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 nonreceptor kinases, proteins, GPCR and ion channels, indicative of a better drug safety profile in terms of clinical relevance. This study including two phases: (1) dose-escalation , this phase using a 3+3design,9-18 patients will be enrolled and receive 25mg/35mg/50mg chiauranib and 1000mg/m2 capecitabine Q3W. (2) dose-expansion,About 20 patients will be enrolled and receive the MTD dose of chiauranib and 1000mg/m2 capecitabine Q3W. This study also to explore the PK variation and gene expression via blood samples

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Triple-negative Breast Cancer
Keywords
Chiauranib;Capecitabine;triple-negative breast cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental: Chiauranib + capecitabine
Arm Type
Experimental
Arm Description
Patients receive the combined treatment of Chiauranib plus capecitabine, 21 days as a cycle until objective disease progression.
Intervention Type
Drug
Intervention Name(s)
Chiauranib
Intervention Description
25mg/35mg/50mg orally once daily
Intervention Type
Drug
Intervention Name(s)
capecitabine
Intervention Description
1000mg/m2 on Days 1-14 in a repeating 21-day cycle
Primary Outcome Measure Information:
Title
ORR(Objective reponse rate)
Description
Overall response rate (ORR) is defined as the percentage of patients with complete or partial response evaluated by RECIST 1.1. Per RECIST 1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame
2years
Secondary Outcome Measure Information:
Title
CBR (Clinical Benefit Rate)
Description
Clinical Benefit Rate (CBR) will be determined by looking at the number of subjects who have either a complete response, partial response, or stable disease for greater than or equal to 24 weeks, per RECIST 1.1
Time Frame
2years
Title
PFS (Progression-free survival)
Description
From date of the first dose of study drug until the date of first documented progression or relapse or date of death from any cause, whichever came first,
Time Frame
2years
Title
DoR (Duration of response)
Time Frame
2years
Title
OS(Overall survival)
Time Frame
2years
Title
AEs
Description
percentage of AEs
Time Frame
2years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All patients must have given signed, informed consent prior to registration on study age ≥ 18 years female Histological or cytological evidence of estrogen-receptor negative (ER-), progesterone receptor negative (PgR-) and human epidermal growth factor-2 receptor negative (HER2-) Breast Cancer by local laboratory testing. Patients with locally advanced inoperable or recurrent/metastatic TNBC and had failed treatment with anthracyclines and taxanes. At least 1 lesion can be accurately measured, as defined by RECIST1.1 Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Laboratory criteria are as follows: 1) Complete blood count: hemoglobin (Hb) ≥90g/L ; absolute neutrophil count (ANC) ≥1.5×109/L ; platelets ≥90×109/L; 2) Biochemistry test: serum creatinine(cr) <1.5×ULN; total bilirubin<1.5×ULN; alanine aminotransferase(ALT) ,aspartateaminotransferase(AST)≤2.5×ULN; (ALT,AST#5×ULN if liver involved) 3) Coagulation test: International Normalized Ratio (INR) < 1.5 9. Life expectancy of at least 3 months Exclusion Criteria: Patients have used any anti-cancer therapy, including adiotherapy, chemotherapy, immunotherapy, target therapy, and other anti-tumor treatments within 28 days before the first dose Patients received vascular endothelial growth factor(VEGF)/vascular endothelial growth factor receptor(VEGFR) inhibitor, like Apatinib, Anlotinib, Fruquintinib, Bevacizumab, etc., or Aurora kinase inhibitors, etc; Patients had treatment of capecitabine (except who received the treatment of capecitabine in Neoadjuvant/ Adjuvant therapy, and Recurrence occurs after 12 months) Has known allegies to Chiauranib, capecitabine or any of the excipients prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer Treatment with an investigational agent/instrument within 28 days prior to first dose of study drug Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 Patients with prior invasive malignancies in the past five years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis Have uncontrolled or significant cardiovascular disease, including: 1) Congestive heart failure, unstable angina pectoris, myocardial infarction within 6 months prior to study entry; arrhythmia, or Left Ventricular Ejection Fraction (LVEF) < 50% requiring treatment with agents during screening stage 2) primary cardiomyopathy(dilated cardiomyopathy, hypertrophic cardiomyocyte, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, et,al) 3) History of significant QT interval prolongation, or Corrected QT Interval (QTc) > 470 ms prior to study entry 4) Symptomatic coronary heart disease requiring treatment with agents 5) History of hypertension treated by≥2 agents, or the Blood pressure(Bp) ≥140/90 mmHg prior to study entry 6) Other condition investigator considered inappropriate 10. CT or MRI of the chest during the screening period shows interstitial lung disease or pulmonary fibrosis or lung inflammation that requires treatment, or within 6 months before the first dose, history of pneumonia requiring oral or intravenous steroid treatment 11. Have clinical significant gastrointestinal abnormality that would impair the ingestion, transportation or absorption of oral agents, history of gastrointestinal perforation or abdominal fistula, peptic ulcer disease within 6 months prior to first dose of study drug 12. Urinary protein ≥ 2+ and quantitative urinary protein ≥ 1g/24 h during the screening period 13. History of active bleeding within the past 2 months, patients with bleeding potential during the screening period, or receiving anticoagulation therapy 14. Pleural fluid, ascites or pericardial effusion with significant symptoms or required treatment of puncture or drainage during the screening period 15. History of deep venous thrombosis or Pulmonary embolism within the past 6 months 16. Active infection requiring oral or intravenous systemic antimicrobial therapy during the screening period 17. Screening for HIV antibody positive 18. Screening test for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive with virus replication, hepatitis C antibody (HCVAb) positive with virus replication 19. Any mental or cognitive disorder, that would impair the ability to understand the informed consent document, or the compliance of study 20. Candidates with drug and alcohol abuse 21. Participants of reproductive potential not willing to use adequate contraceptive measures for the duration of the study.Pregnant or breastfeeding women 22. Any other condition which is inappropriate for the study in the opinion of the investigators
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yu Chen
Phone
8610-56102349
Email
chenyu@chipscreen.com
First Name & Middle Initial & Last Name or Official Title & Degree
Zefei Jiang, Study Principal Investigator
Email
jiangzefei@csco.org.cn
Facility Information:
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shusen Wang
Email
wangshs@sysucc.org.cn
Facility Name
Henan Cancer Hospital
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450003
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Min Yan
Email
ym200678@126.com
Facility Name
Jiangsu Province Hospital
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210029
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yongmei Yin
Email
ym.yin@hotmail.com
Facility Name
The Fifth Medical Center of PLA General Hospital
City
Beijing
State/Province
Other (Non U.s.)
ZIP/Postal Code
10010
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zefei Jiang
Email
jiangzefei@csco.org.cn

12. IPD Sharing Statement

Plan to Share IPD
No

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A Phase II Study of Chiauranib in Combine With Capecitabine in TNBC

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