Study of Vitamin D in Untreated Metastatic Colorectal Cancer
Condition: Metastatic Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: FOLFOX + bevacizumab; Vitamin D
Intervention MeSH terms: Vitamin D; Leucovorin; Bevacizumab; Fluorouracil; Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 139.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: previously untreated

Summary:

      This is a prospective, randomized, double-blind phase II trial to evaluate the efficacy and
      safety of two doses of vitamin D supplementation in combination with standard chemotherapy in
      participants with previously-untreated metastatic colorectal adenocarcinoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed adenocarcinoma of the colon or rectum that is metastatic or
             locally advanced (unresectable)

          -  Measurable disease

          -  KRAS wild-type and KRAS mutant patients are eligible

          -  No prior systemic treatment for advanced or metastatic colorectal cancer is allowed

          -  No prior radiotherapy to more than 25% of bone marrow

          -  No surgery or major biopsy within 4 weeks of randomization

          -  Paraffin-embedded and/or snap-frozen tumor tissue samples must be available

        Exclusion Criteria:

          -  Not pregnant or breastfeeding

          -  No prior chemotherapy, systemic therapy or investigational agent

          -  No concurrent use of other anti-cancer therapy

          -  No known brain metastases

          -  No history of other malignancies except adequately treated non-melanoma skin cancer,
             curatively treated in situ cancer of the cervix, curatively treated lobular or ductal
             carcinoma in situ of the breast or other cancer curatively treated with no evidence of
             disease for more than 3 years prior to randomization

          -  No regular use of vitamin D supplements greater than 2000 IU per day in the past year

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to 5-FU, capecitabine, oxaliplatin, leucovorin, bevacizumab
             and/or vitamin D3

          -  No significant history of bleeding events, pre-existing bleeding diathesis,
             coagulopathy or gastrointestinal perforation

          -  No arterial thrombotic events within 6 months of randomization

          -  No serious non-healing wound, ulcer or bone fracture

          -  No history of uncontrolled hypertension

          -  No clinically significant peripheral neuropathy

          -  No predisposing colonic or small bowel disorders in which the symptoms are
             uncontrolled

          -  No uncontrolled seizure disorder or active neurological disease

          -  No pre-existing hypercalcemia

          -  No known active hyperparathyroid disease

          -  No regular use of thiazide diuretics

          -  No malabsorption, uncontrolled vomiting or diarrhea

          -  No known co-morbid disease that would increase the risk of toxicity

          -  No use of chronic oral corticosteroid therapy or any other therapy that can cause
             vitamin D depletion

          -  No clinically significant cardiovascular disease

          -  No uncontrolled intercurrent illness

          -  No history of any medical or psychiatric condition or addictive disorder or laboratory
             abnormality that may increase the risks associated with study participation