Capecitabine + Irinotecan Followed by Combined Modality Capecitabine and Radiation in Locally Advanced Rectal Cancer
Condition: Rectal Cancer
MeSH terms: Rectal Neoplasms
Intervention: Capecitabine; Irinotecan; EUS; Neoadjuvant Chemotherapy; Preoperative Radiation; Surgery; Adjuvant Chemotherapy
Intervention description: Capecitabine 1000* mg/m2 po bid day 1-14; repeat every three weeks for two cycles
*For calculated creatinine clearance of 30-50 mL/min or patients > 70 years old, capecitabine starting dose is 825 mg/m2 po bid; Irinotecan 200 mg/m2 IV, day 1; biopsy per EUS; Irinotecan 200 mg/m2 IV, day 1
Capecitabine 1000 mg/m2 po bid day 1-14; repeat every three weeks for two cycles; Pelvic XRT 45 Gy/1.8 GY/fx/qd+5/4 Gy/1.8 Gy/fx/qd for T3+9 Gy/1.8/Gy/fx/qd for T4; Surgery within 8 weeks following chemoradiotherapy; Adjuvant chemotherapy at investigator's discretion
Intervention MeSH terms: Capecitabine; Irinotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Rectal Cancer

Summary:

      Preoperative induction chemotherapy has been successfully used in a variety of malignancies
      and provides several advantages over postoperative therapy. Combination of
      5-FU/Leucovorin/CPT-11 has demonstrated significantly better response rate than
      5-FU/Leucovorin alone. Replacing 5-FU with oral capecitabine in combination with CPT-11 has
      emerged as a potentially more effective, safe and convenient treatment option for metastatic
      colorectal cancer. Capecitabine is also well tolerated in concurrent treatment with
      radiation. Recent data has shown that preoperative radiation appears to be significantly more
      effective in increasing resectability rates.

      This trial will investigate the activity of capecitabine and CPT-11 combination in the
      preoperative setting followed by chemoradiation with capecitabine in locally advanced rectal
      cancer to improve response and decrease local recurrence. We will also study whether TS, TP,
      DPD and carboxyesterase expressions correlate with the objective response rate with this
      chemotherapy and chemoradiation regimen.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed adenocarcinoma of the rectum < 15 cm from the anal verge
             without evidence of distant metastasis·

          -  Measurable disease. ·

          -  Either mobile cancers (with clinical stage T3 or T4 by endorectal ultrasound) or fixed
             cancer (defined as clinical T4 for this study) on palpation. ·

          -  Malignant disease may not extend to the anal canal (across the dentate line)

        Exclusion Criteria:

          -  No prior chemotherapy or radiation therapy to the pelvis.

          -  Patients with clinical stage T 1-2, N0 rectal cancer who are candidates for primary
             resection are not eligible·

          -  No synchronous colonic cancer unless the synchronous tumor is Tis or T1 and has been
             completely resected·

          -  Patients must not be taking warfarin·

          -  No prior unanticipated severe reaction to fluoropyrimidine therapy, or known
             sensitivity to 5-Fluorouracil or known DPD deficiency.·

          -  No known existing uncontrolled coagulopathy·

          -  Negative pregnancy test·

          -  No current breastfeeding·

          -  No serious concomitant systemic disorders incompatible with the study· No prior
             malignancies with the exception of curatively treated basal or squamous carcinoma of
             the skin, carcinoma in-situ of the cervix, or any other cancer for which the patient
             has been disease-free for < 5 years.·

          -  Patients must not be treated with any of the following while on protocol therapy or
             within 28 days prior to beginning protocol therapy: sorivudine, brivudine, cimetidine,
             allopurinol.

          -  Patients on dilantin must have regular monitoring of dilantin levels.