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

Hengrui Medicine

Status and phase

Completed

Phase 2

Conditions

Colorectal Cancer

Treatments

Drug: apatinib

Drug: Apatinib

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01531777

APTN-II-CRC

Details and patient eligibility

About

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.

Enrollment

40 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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