This randomized phase II trial studies how well radiation therapy and capecitabine with or without curcumin before surgery works in treating patients with rectal cancer. Drugs such as curcumin may make tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether chemotherapy and radiation therapy is more effective with or without curcumin when given before surgery in 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
22
Given PO
Given PO
Correlative studies
Optional correlative studies
Given PO
Ancillary studies
Undergo radiation therapy
M D Anderson Cancer Center
Houston, Texas, United States
Number of Participants With Pathologic Complete Response (pCR) Rate
Compared the rate of pCR between treatment arms with Fisher's exact test.
Time frame: At time of surgery
Change in Curcumin Level in Tumor Tissue
A logistic regression model with pCR as the dependent variable will be used to assess the association between pCR and NF-kB activity and treatment.
Time frame: Baseline to 11.5 weeks
Change in Curcumin Level in Serum
Plasma levels were assessed pre and post curcumin/placebo administration. During week 2 (after at least 5 fractions of radiation therapy) of chemoradiation therapy: 1. Optional endoscopic biopsy 2. Optional blood collection for pharmacology (1 hour before and 1 hour after intake of curcumin or placebo)
Time frame: assessed 1 hr pre/post curcumin administration on one of the days during week 2 of radiation therapy (fractions 6-10)
Tumor Regression Grade
tumor regression grade (1= pCR, 2= near pCR, 3= partial response, 4= no response, 5=progression).
Time frame: Baseline to 11.5 weeks
Overall Survival (OS)
OS was calculated from start of CRT to date of death, censored at last follow-up. Estimated with the Kaplan-Meier method.
Time frame: 5 years
Progression Free Survival (PFS)
PFS was calculated from start of CRT to date of disease progression or death, censored at last endoscopy/imaging evaluation.
Time frame: 5 years
Number of Participants With Tumor Downstaging
Tumor downstaging (DS) is defined as a decrease in the T stage of the primary tumor by at least 1.
Time frame: Baseline to 11.5 weeks
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