bevacizumab-containing regimen for metastatic colorectal cancer failed to cytotoxic treatment

Conditions: Neoplasm; Colorectal Cancer; Metastatic Neoplasm

Summary: bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (vegf), combined with fluoropyrimidine-based chemotherapy is now the standard first and second-line treatment for metastatic colorectal cancer. the efficacy of bevacizumab with cytotoxic agents in the third-line treatment of patients with mcrc is still unknown.

this is a single arm, phase ii, open-labelled clinical trial to evaluate the safety and efficacy of bevacizumab combined with cytotoxic agents in the treatment of patients with mcrc progressing under all available cytotoxic chemotherapy

Eligibility criteria:
inclusion criteria: * signed informed consent obtained. * subjects must be able to understand and willing to sign a written informed consent. * subjects \> 18 years of age * subjects must have an eastern cooperative oncology group (ecog) performance status of 0 or 2. * histological or cytological diagnosis of adenocarcinoma of the colon or rectum. * subjects have unresectable metastatic lesions. * subjects failed to respond to oxaliplatin, irinotecan and fluorouracil. * subjects have at least one measurable lesion according to response evaluation criteria in solid tumors (recist) criteria measured within 4 weeks prior to registration. * leukocytes ≥ 3.0 x109/ l, absolute neutrophil count (anc) ≥ 1.5 x109/ l, platelet count ≥ 100 x109/ l, hemoglobin (hb) ≥ 9g/ dl. * total bilirubin ≤1.5 x the upper limit of normal (uln). * alanine aminotransferase (alt) and aspartate aminotransferase (ast) ≤ 5 x uln. * amylase and lipase ≤ 1.5 x the uln. * serum creatinine ≤ 1.5 x the uln. * calculated creatinine clearance or 24 hour creatinine clearance ≥ 50 ml/ min. exclusion criteria: * any previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to this study. * extended field radiotherapy within 4 weeks or limited field radiotherapy within 2 weeks prior to randomization. * major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks before start of study medication. * uncontrolled hypertension. (systolic blood pressure \> 150 mmhg or diastolic pressure \> 90 mmhg despite optimal medical management). * significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment or a history of ventricular arrhythmia * arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication. * any evidence of active infection. * known history of human immunodeficiency virus (hiv) infection. * history of bleeding diathesis or coagulopathy. * history of interstitial pneumonitis or pulmonary fibrosis * pregnancy or lactation at the time of study entry. * any history of or currently known brain metastases. * known dihydropyrimidine dehydrogenase (dpd) deficiency * any illness or medical conditions that are unstable or could jeopardize the safety of the subjects and his/her compliance in the study. * subjects with known allergy to the study drugs or to any of its excipients. * current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.

Keywords: bevacizumab refractory colorectal cancer metastatic