High-Dose Cholecalciferol in Treating Patients Receiving Combination Chemotherapy and Bevacizumab as First-Line Therapy For Metastatic Colorectal Cancer
Condition: Stage IV Colon Cancer; Stage IV Rectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: leucovorin calcium; bevacizumab; cholecalciferol; fluorouracil; oxaliplatin; pharmacological study
Intervention description: Given IV; Given IV; Given PO; Given IV; Given IV; Correlative studies
Intervention MeSH terms: Vitamin D; Cholecalciferol; Leucovorin; Bevacizumab; Antineoplastic Agents, Immunological; Fluorouracil; Oxaliplatin; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 79 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving high-dose cholecalciferol works in treating
      patients receiving combination chemotherapy and bevacizumab as first-line therapy for
      metastatic colorectal cancer. Cholecalciferol during treatment may delay the development of
      colorectal cancer. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and
      oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the
      cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can
      block tumor growth in different ways. Some block the ability of tumor cells to grow and
      spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
      Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor.
      Giving cholecalciferol together with combination chemotherapy and monoclonal antibody therapy
      may be an effective treatment for colorectal cancer
    

Eligibility criteria:

        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