Expired Study
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Boston, Massachusetts 02215


Purpose:

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


Study summary:

PRIMARY OBJECTIVES: I. To compare the overall survival of patients treated with irinotecan, 5-FU and leucovorin versus those treated with oxaliplatin, leucovorin and 5-FU versus those treated with leucovorin and 5-FU for patients with stage II and III rectal cancer. SECONDARY OBJECTIVES: I. To prospectively assess rectal function using the Patient Bowel Function/Uniscale questionnaire and the FACT Diarrhea Subscale in patients treated with an adjuvant program of pelvic radiation therapy and chemotherapy. II. To correlate TS, DPD and TP expression (key targets for 5-FU); retention of chromosome 18q alleles and MSI with TGFβ1RII mutation (markers for 5-FU efficacy); ERCC1, ERCC2 and XPF expression (participants in repair of adducts from oxaliplatin); and p53 gene mutation in tumor tissue specimens with treatment efficacy. III. To correlate tumor molecular prognostic markers (chromosome 18q allelic loss and MSI) with survival. IV. To determine physician preference in regard to the radiation-chemotherapy sequence in the Intergroup. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG performance status (0 vs 1), chemotherapy/radiotherapy sequence (preoperative vs postoperative), and risk group (high risk [T3, N+, M0 or T4, any N, M0] vs low risk [T1-2, N+, M0 or T3, N0, M0]). Patients are treated in 1 of 2 groups according to physician preference and then randomized to 1 of 3 treatment arms. GROUP I (preoperative chemoradiotherapy and additional adjuvant chemotherapy): Preoperative chemoradiotherapy: Patients receive 1 of 3 treatment regimens, determined by the treating physician. REGIMEN A (radiotherapy and fluorouracil): Patients undergo external beam radiotherapy once daily 5 days a week for 5 1/2 weeks (total of 28 fractions). Patients also receive concurrent fluorouracil IV continuously 7 days a week for 5 1/2 weeks. REGIMEN B (radiotherapy, fluorouracil, and leucovorin calcium): Patients undergo external beam radiotherapy as in regimen A. Patients also receive concurrent fluorouracil IV and leucovorin calcium IV continuously for 4 days on weeks 1 and 5. REGIMEN C (radiotherapy and capecitabine)*: Patients undergo external beam radiotherapy as in regimen A. Patients also receive concurrent oral capecitabine twice daily for 5 1/2 weeks. NOTE: *Regimen C is allowed only for patients enrolled on protocol NSABP-R-04. Surgery: Within 21-56 days after the completion of chemoradiotherapy, patients undergo surgical resection. Additional adjuvant chemotherapy: Within 21-56 days after complete surgical resection, patients are randomized to 1 of 3 treatment arms. ARM I: Patients receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours followed immediately by fluorourcil IV bolus on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 8 courses. ARM II: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours followed immediately by fluorourcil IV bolus on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 8 courses. ARM III: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV over 1 hour on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 8 weeks for 3 courses. In all arms, treatment continues in the absence of disease progression or unacceptable toxicity. GROUP 2 (postoperative chemoradiotherapy and additional adjuvant chemotherapy): Within 21-56 days after complete surgical resection, patients are randomized to 1 of 3 treatment arms. ARM I: Patients receive irinotecan, leucovorin calcium, and fluorouracil as in group 1, arm I for 4 courses. ARM II: Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in group 1, arm II for 4 courses. ARM III: Patients receive leucovorin calcium and fluorouracil as in group 1, arm III for 1 course. Within 4 weeks after the completion of chemotherapy, all patients undergo concurrent pelvic chemoradiotherapy as described in group 1 preoperative chemoradiotherapy Regimen A, B, or C, followed 4-6 weeks later by 4 additional courses of adjuvant chemotherapy for arms I and II and 2 additional courses of adjuvant chemotherapy for arm III. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually for 5 years.


Criteria:

Inclusion Criteria: - GROUP I: Patients must have histologically proven adenocarcinoma of the rectum with no distant metastases; clinical staging is required (T3N0M0, T4N0M0, TanyN1-3M0) - GROUP I: Patients must not have evidence of tumor outside of the pelvis including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy - GROUP I: Patients must have ECOG performance status 0-1 - GROUP I: The distal border of the tumor must be 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 surgery are eligible regardless of the distance determined by endoscopy - GROUP I: Transmural penetration of tumor through the muscularis propria must be demonstrated by CT scan, endo-rectal ultrasound or MRI - GROUP I: 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 - GROUP I: 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 - GROUP I: Patients must not have received prior chemotherapy or pelvic irradiation therapy - GROUP I: 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 more than five years - GROUP I: Patients must not have an active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy - GROUP I: Female patients must not be pregnant or breast-feeding; all females of childbearing potential must have a blood or urine test within 2 weeks prior to registration to rule out pregnancy - GROUP I: Sexually-active women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception - GROUP II: Patients must have had histologically proven adenocarcinoma of the rectum with no distant metastases; pathologic staging is required (T3N0M0, T4N0M0, TanyN1-3M0) - GROUP II: Patients must not have evidence of tumor outside of the pelvis including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy - GROUP II: Patients must have ECOG performance status 0-1 - GROUP II: 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 - GROUP II: Patients must not have received prior chemotherapy or pelvic irradiation therapy - GROUP II: 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 more than five years - GROUP II: Patients must not have an active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy - GROUP II: Female patients must not be pregnant or breast-feeding because of the potentially teratogenic and abortifacient effects of this regimen and there is no information on the excretion of the agents or their metabolites into breast milk; all females of childbearing potential must have a blood or urine test within 2 weeks prior to registration to rule out pregnancy - GROUP II: Sexually active women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception - RANDOMIZATION: Patients must have a completely resected tumor and be within 21 - 56 days from the date of surgery - RANDOMIZATION: Patients who received combination chemotherapy/radiation prior to randomization (Group I) must have had a minimum radiation dose of 50.4 Gy - RANDOMIZATION: Patients must have ECOG performance status 0-1 - RANDOMIZATION: Creatinine =< 1.5 x ULN obtained =< 4 weeks prior to randomization - RANDOMIZATION: Bilirubin =< 1.5 x ULN - RANDOMIZATION: SGOT (AST) =< 3 x ULN obtained =< 4 weeks prior to randomization - RANDOMIZATION: Absolute neutrophil count >= 1500/mm3 - RANDOMIZATION: Platelet count >= 100,000/mm3 =< 4 weeks prior to randomization - RANDOMIZATION: Patients must not have an active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy


NCT ID:

NCT00068692


Primary Contact:

Principal Investigator
Al Benson
Eastern Cooperative Oncology Group


Backup Contact:

N/A


Location Contact:

Boston, Massachusetts 02215
United States



There is no listed contact information for this specific location.

Site Status: N/A


Data Source: ClinicalTrials.gov

Date Processed: December 11, 2017

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