High-Dose Cholecalciferol in Treating Patients Receiving Combination Chemotherapy and Bevacizumab as First-Line Therapy For Metastatic Colorectal Cancer

This is an interventional treatment trial for Stage IV Colon Cancer Read More

Inclusion Criteria:

• Patients should have untreated metastatic colorectal cancer; prior adjuvant chemotherapy is allowed as long as the development of metastatic disease occurred more than 6 months from completion of adjuvant treatment
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Platelets >= 100,000/mm^3
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Hemoglobin > 9 gm/dl
• Calculated creatinine clearance > 40 ml/min according to the Cockcroft-Gault formula OR per 24 hour urine collection
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x institutional upper normal level if no liver metastases and < 5 x upper limit of normal (ULN) in the setting of liver metastases
• Total bilirubin =< 1.5 x institutional upper normal level
• Albumin >= 2.5 g/dl
• Urine protein:creatinine (UPC) ratio < 1; in the event UPC is > 1, the patient will require a 24-hr urine protein and will be eligible if 24-hr urine collection has < 1,000 mg protein
• Patients of child-hearing potential must agree to use acceptable contraceptive methods (e.g., double harrier) during treatment
• Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board-approved written informed consent form prior to receiving any study-related procedure
• Presence of measurable disease defined as a lesion >= 1 cm by computed tomography (CT); all sites of disease should be evaluated =< 3 weeks before treatment initiation
• Baseline 25-D3 level of < 40 ng/ml

Exclusion Criteria:

• Patients may not be receiving any other investigational agents that are not included in this study
• Patients with known brain metastases
• History of other invasive cancers with the exception of the following: a. Curatively resected or treated non-melanoma skin cancer; b. Curatively treated cervical carcinoma in situ; c. Other primary solid tumors treated curatively and no treatment administered >= 2 years before enrollment, and in the investigator opinion, it is unlikely that there will be a recurrence =< 1 year post enrollment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to oxaliplatin, 5-FU, leucovorin, bevacizumab, and vitamin D3 and other agents used in study
• History of clinically significant bleeding within 6 months of enrollment
• Clinically significant cardiovascular disease within 12 months prior to enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on this study
• Major surgery within 28 days prior to enrollment or still recovering from prior surgery
• Known dihydropyrimidine dehydrogenase (DpD) deficiency
• History or evidence upon physical examination of central nervous system (CNS) disease (e.g., primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of stroke)
• Serious, nonhealing wound, ulcer, or bone fracture
• Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 95 mmHg despite medications)
• History of arterial thrombosis within the last 12 months
• History of visceral arterial ischemia
• Subjects unwilling or unable to comply with study requirements
• Any condition that in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug
• Received an investigational agent within 30 clays prior to enrollment
• Treatment with vitamin D replacement with doses exceeding an average of 1000 IU/day (vitamin D3) within 60 days prior to enrollment