Paricalcitol, Fluorouracil, and Radiation Therapy in Treating Patients With Rectal Cancer That Can Be Removed in Surgery

PRIMARY OBJECTIVES:

I. To evaluate toxicity and tolerability of oral paricalcitol at 2 μg/day when
co-administered with oral 5-fluorouracil (fluorouracil)-based chemoradiation in patients with
histologically confirmed, resectable T3-T4 adenocarcinoma of rectal mucosal origin or
node-positive disease with no known distant metastases.

SECONDARY OBJECTIVES:

I. To study the biologic effects of oral paricalcitol in addition to oral 5-fluorouracil
chemoradiation on Vitamin D receptor staining, MIB-1, Caspase 3, P 21, and Bax protein
expression in these patients.

II. To identify patterns of gene expression in tumor samples of patients who receive chemo
radiation with and without Paricalcitol supplementation using gene microarray technology.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive paricalcitol orally (PO) daily. Patients also receive standard care
chemoradiotherapy with fluorouracil PO.

ARM II: Patients receive standard care chemoradiotherapy as in Arm I.

In both arms, treatment continues until surgical resection in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 1 month after surgery.

Inclusion Criteria:

Patients must have histologically confirmed T3-T4 adenocarcinoma of rectal mucosal origin
or node positive, with no confirmed distant metastases, and that has been shown to be
resectable Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Leukocytes >=
3,000/mcL Absolute neutrophil count >= 1,500/mcL Platelets >= 100,000/mcL Total bilirubin
within normal institutional limits Aspartate aminotransferase (AST) (serum glutamic
oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate
transaminase [SGPT]) =< 2.5 X institutional upper limit of normal Creatinine within normal
institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with
creatinine levels above institutional normal Patients must not have deficient levels of
Vitamin D, 1, 25 Hydroxy as defined by the institution (this allows patients with normal
vitamin D or insufficient vitamin D) Ability to understand and the willingness to sign a
written informed consent document

Exclusion Criteria:

No prior pelvic radiation therapy or chemo-radiation to the rectum; no chemo-radiation for
any other reason in the last 8 weeks Patients may not be receiving any other
investigational agents Patients with a history of or current hypercalcemia may not be
enrolled in this study History of allergic reactions attributed to compounds of similar
chemical or biologic composition to paricalcitol 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 would limit compliance with study requirements Pregnant women and nursing
mothers are excluded from this study because the adverse effects on the fetus from chemo
radiation Human immunodeficiency virus (HIV)-positive patients on combination
antiretroviral therapy are ineligible because of the potential for pharmacokinetic
interactions with these agents; in addition, these patients are at increased risk of lethal
infections when treated with marrow-suppressive therapy; appropriate studies will be
undertaken in patients receiving combination antiretroviral therapy when indicated