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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01531777
• Other study ID #: APTN-II-CRC
• Status: Completed
• Phase: Phase 2
• First received: February 7, 2012
• Last updated: April 2, 2015
• Start date: April 2011
• Est. completion date: November 2014

Study information

• Verified date: February 2012
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• Apatinib
500 mg,p.o.,qd, until disease progression or intolerable toxicity or patients withdrawal of consent.
• apatinib
750 mg,p.o.,qd, until disease progression or intolerable toxicity or patients withdrawal of consent.

Locations

Country	Name	City	State
China	Fudan University cancer hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Jiangsu HengRui Medicine Co., Ltd.	Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ORR (Objective Response Rate)		12 weeks	No
Secondary	DCR (Disease Control Rate)		12 weeks after treatment	No
Secondary	PFS		3 years	No
Secondary	OS (Overall Survival)		3 years	No
Secondary	QoL (Quality of Life)		3 years	Yes