Study to Identify Transcriptional Targets of Vitamin D in Patients With Stage I-III Colon Cancer or Resectable Colon Cancer Liver Metastases Receiving Preoperative Vitamin D Supplementation.
This study seeks to learn more about the vitamin D receptor and its relationship to colon cancer. The Vitamin D receptor is found in colon cancer cells. When Vitamin D binds to the receptor in the cancer cells, it may stop cancer cells from growing abnormally and may cause cancer cell death. Vitamin D has been used in other research studies and information from those other research studies suggests that Vitamin D may help in the treatment of colon cancer. Participants will receive either high-dose vitamin D or standard-dose vitamin D. The study drug will be given 14-28 days prior to your surgery. The number of days will depend on when the surgery is scheduled.
∙ Participants must meet the following criteria on screening examination to be eligible to participate in the study:
• Participants must have histologically confirmed adenocarcinoma of the colon that is localized, with no evidence of distant metastasis (stage I, II, or III), and for which surgical resection of the primary tumor is being planned;
⁃ -OR
• Participants must have histologically or cytologically confirmed adenocarcinoma of the colon with resectable liver metastases for which liver resection is being planned.
• No prior radiation therapy or systemic treatment is allowed for patients undergoing resection of stage I, II, or III colon cancer.
• Prior systemic treatment or radiation therapy is allowed for patients with resectable liver metastases.
‣ The last dose of chemotherapy or radiation must have been administered at least 4 weeks prior to liver surgery.
⁃ The last dose of bevacizumab must have been administered at least 6 weeks prior to liver resection.
• Age ≥18 years.
• ECOG performance status ≤ 1 (see Appendix A)
• Participants must have normal organ and marrow function as defined below:
‣ Total bilirubin ≤1.5× institutional upper limit of normal (ULN)
⁃ AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN, or \<5x ULN if clearly attributable to liver metastases
⁃ Serum calcium (corrected for albumin level) ≤ 1x institutional ULN
⁃ Serum creatinine within normal institutional limits or creatinine clearance ≥60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal.
• Participants on full-dose anticoagulation are eligible if the following criteria are met:
‣ Participant has an in-range INR (usually 2-3) on a stable dose of warfarin or is on a stable dose of low molecular weight heparin
⁃ Participant has no active bleeding or pathological condition that carries a high risk of bleeding (i.e., tumor involving major vessels or known varices)
⁃ Participants receiving anti-platelet agents are eligible. In addition, patients who are on daily prophylactic aspirin or anticoagulation for atrial fibrillation are eligible.
⁃ Discontinuation of anticoagulation, aspirin, and/or anti-platelet agents prior to surgery will occur according to institutional standards of care.
• Non-pregnant and not nursing
‣ Women of child-bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 14 days prior to study entry. Women of child-bearing potential include any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea ≥12 consecutive months; or women on hormone replacement therapy with documented serum follicle stimulating hormone level \>35 mIU/mL). Women who are using oral, implanted, or injectable contraceptive hormones or mechanical products such as intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or who are practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child-bearing potential.
⁃ The effects of higher-dose vitamin D3 and colon or liver surgery (and associated perioperative medications and anesthesia) on the developing human fetus are unknown and may pose unacceptable risk. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.