Dose Finding and Pharmacokinetics/Pharmacodynamics Study of Apatinib in the Treatment of Advanced Colorectal Cancer
Primary Purpose
Colorectal Cancer
Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Apatinib
apatinib
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring Advanced Colorectal Cancer
Eligibility Criteria
Inclusion Criteria:
- ≥ 18 and ≤ 70 years of age
- Histological confirmed advanced or metastatic colorectal Cancer,at least one measurable lesion, larger than 10 mm in diameter by spiral CT scan(scanning layer ≤ 5 mm )
- Have failed for ≥ 2 lines of chemotherapy
- Life expectancy of more than 3 months
- ECOG performance scale ≤ 1
- Duration from the last therapy is more than 6 weeks for nitroso or mitomycin More than 4 weeks for operation, radiotherapy or cytotoxic agents
- Adequate hepatic, renal, heart, and hematologic functions (platelets > 80 × 10E+9/L, neutrophil > 1.5 × 10E+9/L, serum creatinine ≤ 1×upper limit of normal(ULN), bilirubin < 1.25 ULN, and serum transaminase ≤ 2.5× ULN)
- Child bearing potential, a negative urine or serum pregnancy test result before initiating apatinib, must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 weeks after the last dose of test article. Male: All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 weeks after the last dose of test article.
- Signed and dated informed consent. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.
Exclusion Criteria:
- History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
- Pregnant or lactating women
- Preexisting uncontrolled hypertension defined as more than 140/90 mmHg despite using single medical therapy, more than class I (NCI CTCAE 3.0 ) myocardial ischemia, arrhythmia(including QTcF:male ≥ 450 ms, female ≥ 470 ms), or cardiac insufficiency myocardial ischemia, arrhythmia, or cardiac insufficiency
- Before or at the same time any, second malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
- Any factors that influence the usage of oral administration Evidence of CNS metastasis
- URT: urine protein ≥ (++)and > 1.0 g of 24 h
- PT, APTT, TT, Fbg abnormal, having hemorrhagic tendency (eg. active peptic ulcer disease) or receiving the therapy of thrombolysis or anticoagulation
- Abuse of drugs
- Certain possibility of gastric or intestine hemorrhage
- Less than 4 weeks from the last clinical trial
- Viral hepatitis type B or type C
- Prior VEGFR inhibitor treatment
- Evidence of significant medical illness that in the investigator's judgment will substantially increase the risk associated with the subject's participation in and completion of the study
Sites / Locations
- Fudan University cancer hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Apatinib 500mg
Apatinib 750mg
Arm Description
500mg,p.o.,qd
750mg,p.o.,qd
Outcomes
Primary Outcome Measures
ORR (Objective Response Rate)
Secondary Outcome Measures
DCR (Disease Control Rate)
PFS
OS (Overall Survival)
QoL (Quality of Life)
Full Information
NCT ID
NCT01531777
First Posted
February 7, 2012
Last Updated
April 2, 2015
Sponsor
Jiangsu HengRui Medicine Co., Ltd.
Collaborators
Fudan University
1. Study Identification
Unique Protocol Identification Number
NCT01531777
Brief Title
Dose Finding and Pharmacokinetics/Pharmacodynamics Study of Apatinib in the Treatment of Advanced Colorectal Cancer
Official Title
A Random, Open, Dose Finding and Pharmacokinetics/Pharmacodynamics(PK/PD) Phase II Study of Apatinib Tablets in the Treatment of Advanced Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
February 2012
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
November 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jiangsu HengRui Medicine Co., Ltd.
Collaborators
Fudan University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
RATIONALE:
Apatinib is a tyrosin-inhibitor agent targeting at vascular endothelial growth factor receptor (VEGFR), and it's anti-angiogenesis effect has been viewed in preclinical tests. The investigators' phase I study has shown that the drug's toxicity is manageable.
PURPOSE:
Studying how well Apatinib works in treating patients.
Finding the efficacy and safety of 500 mg or 750mg Apatinib.
Pharmacokinetics/Pharmacodynamics(PK/PD).
Exploring new outcome measures of antiangiogenic drugs.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
Advanced Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Apatinib 500mg
Arm Type
Experimental
Arm Description
500mg,p.o.,qd
Arm Title
Apatinib 750mg
Arm Type
Experimental
Arm Description
750mg,p.o.,qd
Intervention Type
Drug
Intervention Name(s)
Apatinib
Intervention Description
500 mg,p.o.,qd, until disease progression or intolerable toxicity or patients withdrawal of consent.
Intervention Type
Drug
Intervention Name(s)
apatinib
Intervention Description
750 mg,p.o.,qd, until disease progression or intolerable toxicity or patients withdrawal of consent.
Primary Outcome Measure Information:
Title
ORR (Objective Response Rate)
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
DCR (Disease Control Rate)
Time Frame
12 weeks after treatment
Title
PFS
Time Frame
3 years
Title
OS (Overall Survival)
Time Frame
3 years
Title
QoL (Quality of Life)
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
≥ 18 and ≤ 70 years of age
Histological confirmed advanced or metastatic colorectal Cancer,at least one measurable lesion, larger than 10 mm in diameter by spiral CT scan(scanning layer ≤ 5 mm )
Have failed for ≥ 2 lines of chemotherapy
Life expectancy of more than 3 months
ECOG performance scale ≤ 1
Duration from the last therapy is more than 6 weeks for nitroso or mitomycin More than 4 weeks for operation, radiotherapy or cytotoxic agents
Adequate hepatic, renal, heart, and hematologic functions (platelets > 80 × 10E+9/L, neutrophil > 1.5 × 10E+9/L, serum creatinine ≤ 1×upper limit of normal(ULN), bilirubin < 1.25 ULN, and serum transaminase ≤ 2.5× ULN)
Child bearing potential, a negative urine or serum pregnancy test result before initiating apatinib, must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 weeks after the last dose of test article. Male: All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 weeks after the last dose of test article.
Signed and dated informed consent. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.
Exclusion Criteria:
History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
Pregnant or lactating women
Preexisting uncontrolled hypertension defined as more than 140/90 mmHg despite using single medical therapy, more than class I (NCI CTCAE 3.0 ) myocardial ischemia, arrhythmia(including QTcF:male ≥ 450 ms, female ≥ 470 ms), or cardiac insufficiency myocardial ischemia, arrhythmia, or cardiac insufficiency
Before or at the same time any, second malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
Any factors that influence the usage of oral administration Evidence of CNS metastasis
URT: urine protein ≥ (++)and > 1.0 g of 24 h
PT, APTT, TT, Fbg abnormal, having hemorrhagic tendency (eg. active peptic ulcer disease) or receiving the therapy of thrombolysis or anticoagulation
Abuse of drugs
Certain possibility of gastric or intestine hemorrhage
Less than 4 weeks from the last clinical trial
Viral hepatitis type B or type C
Prior VEGFR inhibitor treatment
Evidence of significant medical illness that in the investigator's judgment will substantially increase the risk associated with the subject's participation in and completion of the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jin Li, MD
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fudan University cancer hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200000
Country
China
12. IPD Sharing Statement
Learn more about this trial
Dose Finding and Pharmacokinetics/Pharmacodynamics Study of Apatinib in the Treatment of Advanced Colorectal Cancer
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