| Eligibility |
Inclusion Criteria:
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.
Exclusion Criteria:
Participants who exhibit any of the following conditions at screening will not be eligible
for admission into the study.
- Prior systemic therapy, radiotherapy, or investigational agent in participants
undergoing surgery for stage I, II, or III colon cancer.
- Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
bevacizumab) of liver resection.
- Concurrent use of other anti-cancer therapy, including chemotherapy agents, targeted
agents, biological agents, immunotherapy, or investigational agents not otherwise
specified in this protocol.
- Inability to swallow pills.
- History of malabsorption or uncontrolled vomiting or diarrhea, or any other disease
significantly affecting gastrointestinal function that could interfere with absorption
of oral medications.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to vitamin D.
- Regular use of supplemental vitamin D totaling = 2,000 IU/day in the past year.
- Use of supplemental vitamin D or supplements containing vitamin D beyond the
protocol-prescribed study treatment is not allowed during the treatment period of
this clinical trial.
- In order to maintain blinding, vitamin D levels should not be routinely checked
at screening or during the study by the treating investigator. Vitamin D levels
will be assayed only as part of the research blood samples collected during the
study. If there are concerns related to a participant's vitamin D status, the
lead Principal Investigator should be contacted for further discussion.
- Use of chronic oral corticosteroid therapy, lithium, phenytoin, quinidine, isoniazid,
and/or rifampin (all of which can cause vitamin D depletion). Short-term use of
corticosteroids as anti-emetic therapy for chemotherapy is permitted.
- Regular use of thiazide diuretics (i.e., hydrochlorothiazide), which can lead to
hypercalcemia, and unwillingness or inability to discontinue or switch to an
alternative anti-hypertensive agent.
- Pre-existing hypercalcemia (defined as baseline serum calcium above the institutional
ULN, corrected for albumin level if albumin is not within institutional limits of
normal).
-- The use of supplemental calcium or supplements containing calcium is prohibited
during the treatment period of this clinical trial.
- Known active hyperparathyroid disease or other serious disturbance of calcium
metabolism in the past 5 years.
- History of symptomatic genitourinary stones within the past year.
- Any uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that, in the opinion of the
investigator, may increase the risks associated with study participation or study
treatment, limit compliance with study requirements, or interfere with the
interpretation of study results.
- Pregnant or nursing women or men/women of child-bearing potential who are unwilling to
employ adequate contraception.
-- Pregnant and nursing women are excluded from this study because there is an unknown
but potential risk of adverse events related to higher-dose vitamin D3 and colon or
liver surgery (and associated perioperative medications and anesthesia) on the human
fetus. Consequently, breastfeeding should be discontinued if the mother is enrolled on
the study.
- History of prior or synchronous malignancy except:
- A malignancy that was treated with curative intent, for which there has been no
known active disease for >3 years prior to randomization, and for which the risk
of recurrence is low as determined by the investigator.
- Curatively treated non-melanoma skin malignancy, cervical cancer in situ, or
prostatic intraepithelial neoplasia without evidence of prostate cancer.
- Known positive test for human immunodeficiency virus (HIV), hepatitis C virus, or
acute or chronic hepatitis B infection.
- Participants with these infections are ineligible because they are at increased
risk of significant complications in the perioperative period, particularly for
active hepatitis B or C patients undergoing liver resection. Appropriate studies
will be undertaken in participants receiving combination antiretroviral therapy
when indicated.
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