Combination Chemotherapy and Intensity-Modulated Radiation Therapy in Treating Patients Undergoing Surgery for Locally Advanced Rectal Cancer
Condition: Colorectal Cancer
MeSH terms: Rectal Neoplasms
Intervention: capecitabine; oxaliplatin; resection; radiation therapy; FOLFOX
Intervention description: 1650 mg/m^2/day orally 5 days/week during radiotherapy.; All patients undergo surgery 4 to 8 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.; Pelvic intensity modulated radiation therapy (IMRT): 45 Gy in 25 fx Three dimensional conformal radiation therapy (3D-CRT) boost: 5.4 Gy in 3 fx to total dose of 50.4 Gy in 28 fx; Postoperative chemotherapy is administered to all patients who have a complete resection of rectal cancer with negative surgical margins and begins within 4-8 weeks following surgical resection, consisting of a total of 9 14-day cycles. Oxaliplatin 85 mg/m^2, IV over 2 hours, day 1.
Leucovorin 400 mg/m^2, IV over 2 hours, day 1. 5-fluorouracil bolus 400 mg/m^2, IV push, day 1. 5-fluorouracil infusion 2400 mg/m^2, IV continuous infusion over 46 hours, day 1.
Intervention MeSH terms: Leucovorin; Capecitabine; Fluorouracil; Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 79.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage III rectal cancer; adenocarcinoma of the rectum

Summary:

      RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor
      cells, either by killing the cells or by stopping them from dividing. Specialized radiation
      therapy that delivers a high dose of radiation directly to the tumor may kill more tumor
      cells and cause less damage to normal tissue. Giving these treatments before surgery may make
      the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving
      chemotherapy after surgery may kill any tumor cells that remain after surgery.

      PURPOSE: This phase II trial is studying the side effects and how well giving combination
      chemotherapy together with intensity-modulated radiation therapy works in treating patients
      undergoing surgery for locally advanced rectal cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Pathologically confirmed diagnosis of adenocarcinoma of the rectum by biopsy technique
             that does not completely excise the lesion (e.g., fine needle aspiration, core needle
             biopsy)

               -  Located up to 12 cm from the anal verge with no extension of malignant disease
                  into the anal canal

               -  Clinically determined to be stage T3 or T4,N0-N2, and M0 tumor as determined by
                  the following assessments:

                    -  Colonoscopy and biopsy within 56 days prior to registration

                    -  History/physical examination (including medication history screen for
                       contraindications) within 56 days prior to registration

                    -  Contrast-enhanced imaging of the abdomen and pelvis either by computed
                       tomography(CT), MRI, or Positron-emission tomography(PET)-CT (whole body
                       preferred) within 56 days prior to registration

                    -  Chest x-ray (or CT) of the chest within within 56 days prior to registration
                       to exclude distant metastases (except for patients who have had whole body
                       PET-CT)

                    -  Transrectal ultrasound (TRUS) within 56 days prior to registration required
                       to establish tumor stage

                         -  TRUS not required if clinical exam, CT of the pelvis, and/or MRI
                            demonstrates T4 lesion

          -  No synchronous primary colon carcinoma

          -  No evidence of distant metastases (M1)

        PATIENT CHARACTERISTICS:

        Inclusion criteria:

          -  Zubrod performance status 0-2

          -  Absolute neutrophil count (ANC) ≥ 1,800/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve hemoglobin ≥ 8.0
             g/dL allowed)

          -  Aspartate aminotransferase (AST) < 2.5 times upper limit of normal (ULN)

          -  Alkaline phosphatase < 2.5 times ULN

          -  Bilirubin ≤ 1.5 times ULN

          -  Creatinine clearance > 50 mL/min

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No prior invasive malignancy except nonmelanoma skin cancer unless disease free for a
             minimum of 3 years

        Exclusion criteria:

          -  Severe, active comorbidity, defined as follows:

               -  Unstable angina and/or congestive heart failure requiring hospitalization within
                  the past 12 months

               -  Transmural myocardial infarction within the past 6 months

               -  Acute bacterial or fungal infection requiring intravenous antibiotics

               -  Chronic obstructive pulmonary disease exacerbation or other respiratory illness
                  requiring hospitalization or precluding study therapy within the past 30 days

               -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

               -  AIDS

               -  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

               -  Known, existing uncontrolled coagulopathy, unless clinically stable on
                  anticoagulation therapy for ≥ 2 weeks

               -  Evidence of peripheral neuropathy ≥ grade 2

          -  Prior allergic reaction to oxaliplatin or capecitabine

          -  Lack of physical integrity of the gastrointestinal tract (i.e., severe Crohn disease
             that results in malabsorption; significant bowel resection that would make one
             concerned about the absorption of capecitabine) or malabsorption syndrome that would
             preclude feasibility of oral chemotherapy (i.e., capecitabine)

          -  Prior systemic chemotherapy for colorectal cancer (prior chemotherapy allowed provided
             it was for a cancer other than colorectal cancer)

          -  Prior radiotherapy to the region of the study cancer that would result in overlap of
             radiotherapy fields

          -  Major surgery within 28 days of study enrollment(other than diverting colostomy
             without tumor resection)

          -  Participation in any investigational drug study within 28 days of study enrollment.

          -  Concurrent cimetidine, amifostine, and/or depot Sandostatin