Radiation Therapy and Capecitabine With or Without Curcumin Before Surgery in Treating Patients With Rectal Cancer

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of a combination of capecitabine and radiation therapy with or
without curcumin in locally advanced rectal cancer as assessed by pathological complete
response rate.

SECONDARY OBJECTIVES:

I. To determine downstaging, local control, disease-free survival and overall survival rates.

II. To determine serum and rectal tumor tissue pharmacology of curcumin and its metabolites
in the above patients and its correlation with clinical response.

III. To identify surrogate molecular markers for curcumin effects. IV. To correlate serum
cytokine levels with quality of life in patients receiving this therapy.

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

ARM I: Patients undergo radiation therapy 5 days a week for a total of 28 fractions. Patients
also receive capecitabine orally (PO) twice daily (BID) on the days of radiation therapy and
curcumin PO BID in weeks 1-11.5.

ARM II: Patients undergo radiation therapy and receive capecitabine as in Arm I. Patients
also receive placebo PO BID in weeks 1-11.5.

After completion of study treatment, patients are followed up at 1 month.

Inclusion Criteria:

- All patients must have clinical stage T3,4 N0,1,2 or T2N1,2 adenocarcinoma of the
rectum; patients will be clinically staged using endorectal ultrasound, pelvic
computed tomography (CT) or magnetic resonance imaging (MRI), and physical examination

- Histology must be confirmed with review by the Department of Pathology at MD Anderson
Cancer Center (MDACC)

- All patients must have no distant metastatic disease in the liver, peritoneum, lungs,
or paraaortic lymph nodes

- Patients must have a performance status (Karnofsky scale) of 70% or greater

- Absolute neutrophil count (ANC) > 1200 cells/mm^3

- Platelets > 100,000/mm^3

- Total serum bilirubin < 2 mg/dl

- Blood urea nitrogen (BUN) < 30 mg/dl

- Creatinine < 1.5 mg/dl or creatinine clearance > 50cc/min (estimated as calculated
with Cockcroft-Gault equation)

- Patients must have signed informed consent indicating that they are aware of the
investigational nature of the study, and are aware that participation is voluntary;
patients must also agree to refrain from use of additional herbal supplements during
the course of the study

- Patients will agree to continue contraception for 30 days from the date of the last
study drug administration; sexually active males must practice contraception during
the study

- Postmenopausal woman must have been amenorrheic for at least 12 months to be
considered of non-childbearing potential

Exclusion Criteria:

- Prior complete course up to 5 Gy of radiotherapy to the pelvis

- Pregnant or lactating woman; women of childbearing potential who have not undergone a
hysterectomy with either a positive or no pregnancy test at baseline; women / men of
childbearing potential not using a reliable and appropriate contraceptive method
(oral, injectable, or implantable hormonal contraceptive; tubal ligation;
intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner)

- Treatment for other carcinomas within the last five years, except cured non-melanoma
skin and treated in-situ cervical cancer

- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing
or requiring IV antibiotics, cardiac disease New York Heart Association (NYHA) class
III or IV, unstable angina pectoris, unstable cardiac arrhythmia or tachycardia (heart
rate > 100 beats/minute), or psychiatric illness/ social situations that would limit
compliance with the study requirements are excluded

- Other serious uncontrolled medical conditions that the investigator feels might
compromise study participation

- Major surgery within 4 weeks of the start of study treatment

- Prior unanticipated severe reaction to fluoropyrimidine therapy or known
hypersensitivity to 5-fluorouracil or capecitabine or curcumin

- Concurrent use of Coumadin other than low dose (1 mg) Coumadin used for line patency;
patients on Coumadin must be changed to Lovenox at least 1 week prior to starting
capecitabine

- Concurrent use of cimetidine, allopurinol, or aluminium hydroxide and magnesium
hydroxide-containing antacids such as Maalox

- Sorivudine and brivudine use within 4 weeks of the start of study treatment