Clinical Study of Apatinib and XELOX Combination Regimen to Treat Colorectal Cancer Patients

Study Overview
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Brief Summary
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This study makes an observation over the objective response rate of Apatinib and XELOX combination regimen in the first-line treatment of metastatic colorectal cancer. All the participants will receive the treatment of Apatinib and XELOX combination regimen.

Detailed Description
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XELOX chemotherapy is an effective therapy for metastatic colorectal cancer as first-line treatment. 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%.

Official Title
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A Phase II Clinical Trial Study on Apatinib and XELOX Combination Regimen in the First-line Treatment of End-stage Colorectal Cancer Patients

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Drug: Apatinib and XELOX combined treatment group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unresectable colorectal cancer confirmed by histological means with measurable indication（a minimum size of 10mm by spiral CT scan，which meets the criteria of RECIST 1.1）. Time interval traced back to the latest administration of xelox and folfox combination must be no less than 1 year. age range: ≥18 and ≤75. ECOG PS scale 0 or 1；expected survival time ≥12 weeks. Sufficient blood function：absolute neutrophil count (ANC) ≥1.5×109/L, platelet count ≥80×109/L and hemoglobin≥9g/dL. Sufficient hepatic function：total bilirubin ≤1.5 times upper normal limit(ULN), AST ≤2.5 times ULN, ALT ≤2.5 times ULN and AKP ≤5 times ULN. *AST,ALT relevant criteria alters into AST ≤5 times ULN and ALT ≤5 times ULN if with hepatic metastasis. sufficient renal function: serum creatinin ≤ULN, creatinine clearance rate ≥60 mL/min Female patients under age 50 with complete uterus must be tested negative for pregnancy within 28 days before enrollment (except for those who suffered amenorrhea for more than 24 months). If the pregnancy test was carried out more than 7 days before the first administration, then the urine pregnancy test is required for validation. (within the 7-day interval before administration) Informed consent subscription. (The consent should be approved by independent Ethics Committee, and signed by patients before any substantial trial is initiated.) Exclusion Criteria: Have got other malignant tumors within last 5 years, excluding basal cell skin cancer and cervical carcinoma in situ that has already been cured. With evidence of CNS metastasis, even if the treatment had been carried out before, patients with doubts of CNS metastasis should be conducted MRI or enhanced CT scan on within 28 days before enrollment for ruling out. AST ≤2.5 times ULN and/or ALT ≤2.5 times ULN Had been treated with chemotherapy for last 12 months Had been treated with radiotherapy (except for palliative radiotherapy with evaluable focus outside radiotherapy field on purpose of alleviating pains) With any uncontrolled systemic disease, including active infection, hypertension without treatment, diabetes mellitus, angina pectoris, congestive heart failure, myocardial infarction, severe arrhythmia requires treatment and hepatic/renal/metabolic diseases Taking experimental treatment from another clinical trial study. Being allergic to any relevant chemotherapy drug. With evidence-proved other diseases, neural or metabolic disorders, physical or lab examination abnormalities, which might be contraindication of study drugs or leading to treating-related lethal complications.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apatinib combined treatment group<br>Apatinib Mesylate Tablets 500 mg P.O.d1-21 and XELOX (oxaliplatin 130mg/㎡ i.v. d1, capecitabine 1000mg P.O. d1-d14) Every 3-week time is a cycle until PD or intolerance of drug toxicity occurs. | Drug: Apatinib and XELOX combined treatment group<br>* Apatinib Mesylate Tablets 500 mg P.O.d1-21 and XELOX (oxaliplatin 130mg/㎡ i.v. d1, capecitabine 1000mg P.O. d1-d14) Every 3-week time is a cycle until PD or intolerance of drug toxicity occurs.<br>* Other names: Apatinib combined treatment group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR=complete response (CR) + partial response (PR) .And expected ORR is 0.55. | up to 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | time from randomization to documented progressive disease or death due to any cause, whichever occurs first | up to 2 years | 
| Overall Survival (OS) |  | up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Apatinib, XELOX Regimen, metastatic colorectal cancer