Comparison of Adjuvant Chemotherapy Regimens in Treating Stage II/III Rectal Cancer
Condition: Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Rectal Carcinoma; Stage IIA Rectal Cancer AJCC v7; Stage IIB Rectal Cancer AJCC v7; Stage IIC Rectal Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7; Stage IVA Rectal Cancer AJCC v7; Stage IVB Rectal Cancer AJCC v7
MeSH terms: Adenocarcinoma; Rectal Neoplasms; Adenocarcinoma, Mucinous; Cystadenocarcinoma; Carcinoma, Signet Ring Cell
Intervention: Radiotherapy; Fluorouracil; Leucovorin Calcium; Oxaliplatin; Irinotecan
Intervention description: Undergo external beam radiation therapy; Given IV; Given IV; Given IV; Given IV
Intervention MeSH terms: Leucovorin; Tetrahydrofolates; Formyltetrahydrofolates; Fluorouracil; Oxaliplatin; Irinotecan; Camptothecin; Levoleucovorin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 225.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: rectal cancer; chemotherapy; irinotecan; oxaliplatin

Summary:

      This randomized phase III trial is comparing the effectiveness of three adjuvant combination
      chemotherapy regimens in treating patients who are receiving radiation therapy and
      fluorouracil either before or after surgery for stage II or stage III rectal cancer. Drugs
      used in chemotherapy, such as irinotecan, fluorouracil, leucovorin, and oxaliplatin, use
      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. It is not yet known which adjuvant
      combination chemotherapy regimen is more effective in treating patients who are receiving
      radiation therapy and fluorouracil either before or after surgery for rectal cancer.
    

Eligibility criteria:

        1. Group I (Pre-operative) Registration

             Inclusion Criteria:

               -  Patients must have histologically proven adenocarcinoma of the rectum with no
                  distant metastases. Clinical staging is required (T3N0M0, T4N0M0, TanyN1-3M0).

               -  Patients must not have evidence of tumor outside of the pelvis including liver
                  metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy.

               -  The distal border of the tumor must be at or below the peritoneal reflection,
                  defined as within 12 cm of anal verge by proctoscopic examination. In addition,
                  patients who have had a portion of their tumors confirmed to be below the
                  peritoneal reflection at the time of surgery are eligible regardless of the
                  distance determined by endoscopy.

               -  Transmural penetration of tumor through the muscularis propria must be
                  demonstrated by CT scan, endo-rectal ultrasound or MRI.

               -  Tumors must be defined prospectively by the surgeon as clinically resectable or
                  not.

                    -  Clinically resectable tumors will be defined by the surgeon as not fixed and
                       completely resectable with negative margins based on the routine examination
                       of the non-anesthetized patient.

                    -  Before pre-op treatment, the surgeon should estimate and record the type of
                       resection anticipated: APR, LAR or LAR/coloanal anastomosis.

               -  The tumor may be clinically fixed or initially not completely resectable,
                  clinical stage T4 N0-2 M0 based on the presence of at least one of the following
                  criteria:

                    -  Clinically fixed tumors on rectal examination with tumor adherent to the
                       pelvic sidewall or sacrum.

                    -  Hydronephrosis on CT scan or IVP or ureteric or bladder invasion as
                       documented by cystoscopy and cytology or biopsy, or invasion into prostate.

                    -  Vaginal or uterine involvement.

               -  Patients must not have a previous or concurrent malignancy, with the exception
                  of:

                    -  Nonmelanoma skin cancer or in situ cervical cancer.

                    -  Treated non-pelvic cancer from which the patient has been continuously
                       disease-free for >5 years.

               -  Patients must have ECOG performance status 0-1.

               -  Patients must be > 18 years of age.

               -  All females of childbearing potential must have a blood or urine test within 2
                  weeks prior to registration to rule out pregnancy.

               -  Sexually-active women of childbearing potential and sexually active males are
                  strongly advised to use an accepted and effective method of contraception

             Exclusion Criteria:

               -  Patients have received prior chemotherapy or pelvic irradiation therapy.

               -  Female patients must not be pregnant or breast-feeding.

               -  Patients have an active inflammatory bowel disease or other serious medical
                  illness which might limit the ability of the patient to receive protocol therapy.

          2. Group II (Post-operative) Registration

             Inclusion Criteria:

               -  Patients must have had histologically proven adenocarcinoma of the rectum with no
                  distant metastases. Pathologic staging is required (T3N0M0, T4N0M0, TanyN1-3M0).

               -  Patients must not have evidence of tumor outside of the pelvis including liver
                  metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy.

               -  The distal border of the tumor must have been at or below the peritoneal
                  reflection, defined as within 12 centimeters of anal verge by proctoscopic
                  examination. In addition, patients who have had a portion of their tumors
                  confirmed to be below the peritoneal reflection at the time of the surgery are
                  eligible regardless of the distance determined by endoscopy.

               -  Patients must not have received prior chemotherapy or pelvic irradiation therapy.

               -  Patients must not have a previous or concurrent malignancy, with the exception
                  of:

                    -  Non-melanoma skin cancer or in situ cervical cancer.

                    -  Treated non-pelvic cancer from which the patient has been continuously
                       disease-free for >5 years.

               -  Patients must have ECOG performance status 0-1.

               -  Patients must be > 18 years of age.

               -  All females of childbearing potential must have a blood or urine test within 2
                  weeks prior to registration to rule out pregnancy.

               -  Sexually active women of childbearing potential and sexually active males are
                  strongly advised to use an accepted and effective method of contraception.

             Exclusion Criteria:

               -  Patients have an active inflammatory bowel disease or other serious medical
                  illness which might limit the ability of the patient to receive protocol therapy.

               -  Female patients are pregnant or breast-feeding.

          3. Randomization (Groups I and II)

        Inclusion Criteria:

          -  Patients must have a completely resected tumor and be within 21-56 days from the date
             of surgery.

          -  Patients who received combination chemotherapy/XRT prior to randomization (Group I)
             must have had a minimum radiation dose of 50.4 Gy.

          -  Patients must have ECOG performance status 0-1.

          -  Patients must have adequate renal function (creatinine < 1.5 x ULN) obtained < 4 weeks
             prior to randomization.

          -  Patients must have adequate hepatic function (bilirubin < 1.5 x ULN, SGOT (AST) < 3 x
             ULN) obtained < 4 weeks prior to randomization).

          -  Patients must have absolute neutrophil count > 1500/mm3 and platelet count >
             100,000/mm3 < 4 weeks prior to randomization.

        Exclusion Criteria:

        • Patients have an active inflammatory bowel disease or other serious medical illness which
        might limit the ability of the patient to receive protocol therapy.