Neoadjuvant Chemoradiotherapy and Adjuvant Chemotherapy in Treating Patients Who Are Undergoing Surgical Resection for Locally Advanced Rectal Cancer
Condition: Colorectal Cancer
MeSH terms: Rectal Neoplasms
Intervention: Radiation Therapy; Capecitabine 1650 mg/m^2/day; Capecitabine 1200 mg/m^2/day; Irinotecan; Oxaliplatin; Surgery; Folinic Acid; Fluorouracil; Oxaliplatin
Intervention description: Pelvic radiation therapy given once daily 5 days a week for 6 weeks, 45 Gy in 25 fractions + boost of 5.4 Gy in 3 fractions for a total dose of 50.4 Gy.; 825 mg/m^2 q12 hours (1650 mg/m^2/day) orally 5 days per week during radiotherapy.; 600 mg/m^2 q12 hours(1200 mg/m^2/day) orally 5 days per week during radiotherapy.; 50mg/m^2 IV over 1 hour on days 1, 8, 22, and 29; 50mg/m^2 IV over 2 hours on days 1, 8, 15, 22, and 29; All patients will undergo surgery four to eight weeks following the completion of radiation therapy. The choice of procedure abdominoperineal resection (APR), low anterior resection (LAR), or LAR/coloanal anastomosis is at the discretion of the surgeon.; 400 mg/m^2 IV over 2 hours Day 1 (postoperatively) ,every 14 days, for nine 14-day cycles.; 5-fluorouracil bolus 400 mg/m^2 IV push Day 1 (postoperatively), every 14 days, for nine 14-day cycles.
5-fluorouracil infusion 2400 mg/m^2 IV continuous infusion over 46 hours, beginning day 1, every 14 days, for nine 14-day cycles.; 85 mg/m^2 IV over 2 hours Day 1 (postoperatively), every 14 days, for nine 14-day cycles.
Intervention MeSH terms: Leucovorin; Folic Acid; Capecitabine; Fluorouracil; Oxaliplatin; Irinotecan; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 146.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage III rectal cancer; adenocarcinoma of the rectum; stage II rectal cancer

Summary:

      RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from
      dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage
      tumor cells. Chemoradiotherapy (combining chemotherapy with radiation therapy) before surgery
      may shrink the tumor so that it can be removed. Giving chemotherapy after surgery may kill
      any remaining tumor cells.

      PURPOSE: This randomized phase II trial is studying two different regimens of neoadjuvant
      chemoradiotherapy and adjuvant chemotherapy and comparing how well they work in treating
      patients who are undergoing surgical resection for locally advanced rectal cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adenocarcinoma of the rectum originating at or below 12 cm from the anal verge without
             evidence of distant metastases

          2. Patient must be 18 years of age or greater.

          3. Potentially resectable en bloc based upon surgeon evaluation

          4. Clinical stages T3 or T4, based upon endorectal ultrasound, or physical examination
             (only acceptable for T4 lesions).

          5. Absolute neutrophil count of > 1500 per microliter and platelet count > 100,000 per
             microliter; aspartate aminotransferase (AST) and alkaline phosphatase < 2.5 X upper
             limit of normal (ULN), bilirubin < = 1.5 ULN, calculated creatinine clearance > 50
             ml/min using Cockcroft-Gault formula:

               -  CrCl male = (140 - age) x (wt. in kg) / (Serum Cr) x 72

               -  CrCl female = 0.85 x (CrCl male)

          6. Zubrod performance status 0-2

          7. No history of other malignancies within 5 years, except non-melanoma skin cancer, in
             situ carcinoma of the cervix, or ductal carcinoma in situ of the breast. Previous
             invasive cancer permitted if disease free at least 5 years.

          8. Signed study-specific informed consent prior to randomization

        Exclusion Criteria:

          1. Any evidence of distant metastasis

          2. Synchronous primary colon carcinomas, except T1 lesions (full colonoscopy not required
             for enrollment)

          3. Extension of malignant disease to the anal canal

          4. Prior radiation therapy to the pelvis

          5. Prior chemotherapy for malignancies

          6. Pregnancy or lactation, (exclusion due to potential adverse effects of therapy). Women
             of childbearing potential with either a positive or no pregnancy test (serum or urine)
             at baseline. Women/men of childbearing potential not using a reliable and appropriate
             contraceptive method. (Postmenopausal women must have been amenorrheic for at least 12
             months to be considered to be of non-childbearing potential.) Patients will agree to
             continue contraception for 30 days from the date of the last study drug
             administration.

          7. Serious, uncontrolled, concurrent infection(s).

          8. Participation in any investigational drug study within 4 weeks preceding the start of
             study treatment.

          9. Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic
             coronary artery disease and cardiac arrhythmias not well controlled with medication)
             or myocardial infarction within the last 12 months.

         10. Evidence of uncontrolled seizures, central nervous system disorders or psychiatric
             disability judged by the investigator to be clinically significant, precluding
             informed consent, or interfering with compliance of oral drug intake.

         11. Other serious uncontrolled medical conditions that the investigator feels might
             compromise study participation.

         12. Major surgery within 4 weeks of the study treatment.

         13. Lack of physical integrity of the upper gastrointestinal tract or malabsorption
             syndrome.

         14. Known, existing uncontrolled coagulopathy.

         15. No concurrent cimetidine allowed.