Dose Finding and Pharmacokinetics/Pharmacodynamics Study of Apatinib in the Treatment of Advanced Colorectal Cancer

Study Overview
=================
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.

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

Conditions
-----------------
Colorectal Cancer

Intervention / Treatment
-----------------
* Drug: Apatinib
* Drug: apatinib


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apatinib 500mg<br>500mg,p.o.,qd | Drug: Apatinib<br>* 500 mg,p.o.,qd, until disease progression or intolerable toxicity or patients withdrawal of consent.<br>|
| Experimental: Apatinib 750mg<br>750mg,p.o.,qd | Drug: apatinib<br>* 750 mg,p.o.,qd, until disease progression or intolerable toxicity or patients withdrawal of consent.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR (Objective Response Rate) |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DCR (Disease Control Rate) |  | 12 weeks after treatment | 
| PFS |  | 3 years | 
| OS (Overall Survival) |  | 3 years | 
| QoL (Quality of Life) |  | 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Advanced Colorectal Cancer