A Phase II Clinical Trial Study on Apatinib and 5-Fu Combination Regimen in the Treatment of Advanced Colorectal Cancer Patients
Trial Snapshot
- Phase
- Phase 2
- Sponsor
- Enrollment
- 42
- Locations
- 1
- Primary Endpoint
- ORR
Study Overview
Brief Summary
This study makes an observation over the objective response rate of Apatinib and 5-Fu combination regimen in the three-line treatment of metastatic colorectal cancer. All the participants will randomly receive the treatment of Apatinib and 5-Fu combination regimen or 5-Fu.
Detailed Description
5-Fu chemotherapy is an effective therapy for colorectal cancer. Apatinib is a small-molecule tyrosine kinase inhibitor (TKI) that highly selectively binds to and strongly inhibits vascular endothelial growth factor receptor 2 (VEGFR-2), with a decrease in VEGF-mediated endothelial cell migration, proliferation, and tumor microvascular density. A phase II trail of Apatinib has been demonstrated that Apatinib is safe to treat the metastatic colorectal cancer and the disease control rate can reach 50%.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Apatinib and 5-Fluorouracil
Apatinib 500 mg qd po.5-Fluorouracil 400mg/m2 iv d1，2400mg-3000mg/m2 civ 46h,q2w.5-Fluorouracil derivatives(Capecitabine 1000mg/m2 bid po d1-d14 q3w.S1 40mg/m2 bid po d1-d14 q3w).
Intervention: Apatinib (Drug)
Apatinib and 5-Fluorouracil
Apatinib 500 mg qd po.5-Fluorouracil 400mg/m2 iv d1，2400mg-3000mg/m2 civ 46h,q2w.5-Fluorouracil derivatives(Capecitabine 1000mg/m2 bid po d1-d14 q3w.S1 40mg/m2 bid po d1-d14 q3w).
Intervention: 5-fluorouracil (Drug)
5-Fluorouracil
5-Fluorouracil 400mg/m2 iv d1，2400mg-3000mg/m2 civ 46h,q2w.5-Fluorouracil derivatives(Capecitabine 1000mg/m2 bid po d1-d14 q3w.S1 40mg/m2 bid po d1-d14 q3w).
Intervention: 5-fluorouracil (Drug)
Outcomes
Primary Outcomes
ORR
Time Frame: From assignment of the first subject to 3 months later after the last participant is recruited.
The percentage of subjects with total number of Complete Response (CR) + total number of Partial Response (PR)
Secondary Outcomes
- PFS(From assignment of the first subject to 3 months later after the last participant is recruited.)
- QoL(From assignment of the first subject to 3 months later after the last participant is recruited.)
- DCR(From assignment of the first subject to 3 months later after the last participant is recruited.)
- OS(From assignment of the first subject until 30 death events observed, up to 2 years.)
Investigators
Hui ting Xu，MD
Deputy Chief Physician
Hubei Cancer Hospital