Phase III Randomized Study of Preoperative vs Postoperative 5-FU/CF/Radiotherapy in Patients with Operable Adenocarcinoma of the Rectum
Chemotherapy and Radiation Therapy Before or After Surgery in Treating Patients With Rectal Cancer That Can Be Surgically Removed
Basic Trial Information
|Phase III||Treatment||Completed||18 to 76||NCI||NSABP-R-03|
I. Compare disease-free and overall survival in patients with operable carcinoma of the rectum treated with preoperative vs. postoperative fluorouracil/leucovorin/radiotherapy. II. Compare the local recurrence rates in patients treated with these 2 regimens. III. Evaluate the response of rectal tumors to preoperative chemoradiotherapy, and correlate response with disease-free and overall survival. IV. Assess the down-staging effect of preoperative chemoradiotherapy on tumor size and pathologic status of regional lymph nodes. V. Estimate the proportion of patients receiving preoperative chemoradiotherapy who can be converted to sphincter-saving surgery from abdominoperineal resection and of those who can be converted from sphincter-saving surgery to local excision alone.
Histologically proven, resectable, invasive rectal adenocarcinoma Tumor palpable on rectal exam or accessible endoscopically Distal border no more than 15 cm from anal verge Diagnosis by surgical or endoscopic biopsy required Majority of tumor must remain after biopsy No excisional biopsy Resectability based on: Tumor moveable on clinical exam without fixation to pelvis or adjacent organs beyond limits of exenteration Enlarged perirectal or pelvic lymph nodes must not be fixed to pelvis No radiographic evidence of metastasis Abdominopelvic CT with biopsy of suspicious areas required Intestinal obstruction allowed provided only treatment is decompressing colostomy Free perforation (free air or fluid in abdomen) not eligible Walled-off perforation allowed Synchronous rectal lesions allowed No synchronous colon tumors No histology other than adenocarcinoma Treatment must begin within 49 days of histologic diagnosis
No prior therapy for rectal cancer except an incisional diagnostic biopsy and a preliminary decompression colostomy
Age: 18 to 76 Performance status: 0-2 Life expectancy: At least 10 years excluding the cancer Hematopoietic: WBC at least 4,000 Platelets at least 100,000 Hepatic: Bilirubin no greater than 1.5 times normal AST or ALT no greater than 1.5 times normal No hepatic disease that would preclude treatment Renal: Creatinine no greater than 1.5 times normal No renal disease that would preclude treatment Cardiovascular: No cardiovascular disease that would preclude treatment Other: No active inflammatory bowel disease No nonmalignant systemic disease that would preclude treatment No psychiatric or addictive disorder that would preclude informed consent No prior or concurrent second malignancy except: Nonmelanomatous skin cancer Adequately treated in situ cervical cancer No pregnant women
It is anticipated that 180 patients/year will be accrued for 5 years. Interim analyses will be conducted q 6 months beginning 2.5 years into the study; if a significant survival benefit is seen in one arm, the study may close early.
Randomized study. Arm I: Single-Agent Chemotherapy with Drug Modulation followed by Radiotherapy plus Single-Agent Chemotherapy/Radiosensitization with Drug Modulation followed by Surgery followed by Single-Agent Chemotherapy with Drug Modulation. Fluorouracil, 5-FU, NSC-19893; with Leucovorin calcium, CF, NSC-3590; followed by pelvic irradiation with megavoltage equipment (minimum energies at least 4 MV, Co60); plus 5-FU/CF; followed by tumor excision; followed by 5-FU/CF. Arm II: Surgery followed by Single-Agent Chemotherapy with Drug Modulation followed by Radiotherapy plus Single-Agent Chemotherapy/Radiosensitization with Drug Modulation followed by Single-Agent Chemotherapy with Drug Modulation. Tumor excision; followed by 5-FU/CF; followed by pelvic irradiation as in Arm I; plus 5-FU/CF; followed by 5-FU/CF.
Roh MS, Colangelo LH, O'Connell MJ, et al.: Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol 27 (31): 5124-30, 2009.[PUBMED Abstract]
Hyams DM, Mamounas EP, Petrelli N, et al.: A clinical trial to evaluate the worth of preoperative multimodality therapy in patients with operable carcinoma of the rectum: a progress report of National Surgical Breast and Bowel Project Protocol R-03. Dis Colon Rectum 40 (2): 131-9, 1997.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations
National Surgical Adjuvant Breast and Bowel Project
Ph: 412-359-3336; 866-680-0004
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.