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

NCT ID: NCT01531777

Last Updated: 2015-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2014-11-30

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:

1. Studying how well Apatinib works in treating patients.

2. Finding the efficacy and safety of 500 mg or 750mg Apatinib.

3. Pharmacokinetics/Pharmacodynamics(PK/PD).

4. Exploring new outcome measures of antiangiogenic drugs.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Apatinib 500mg

500mg,p.o.,qd

Group Type: EXPERIMENTAL

Apatinib

Intervention Type: DRUG

500 mg,p.o.,qd, until disease progression or intolerable toxicity or patients withdrawal of consent.

Apatinib 750mg

750mg,p.o.,qd

Group Type: EXPERIMENTAL

apatinib

Intervention Type: DRUG

750 mg,p.o.,qd, until disease progression or intolerable toxicity or patients withdrawal of consent.

Interventions

Apatinib

500 mg,p.o.,qd, until disease progression or intolerable toxicity or patients withdrawal of consent.

Intervention Type: DRUG

apatinib

750 mg,p.o.,qd, until disease progression or intolerable toxicity or patients withdrawal of consent.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: collaborator

Jiangsu HengRui Medicine Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jin Li, MD

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Fudan University cancer hospital

Shanghai, Shanghai Municipality, China

Countries

China

Other Identifiers

APTN-II-CRC

Identifier Type: -

Identifier Source: org_study_id