This phase II trial studies how well giving bevacizumab, radiation therapy, and combination chemotherapy works in treating patients who are undergoing surgery for locally advanced nonmetastatic rectal cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as capecitabine, may make tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy, such as capecitabine, oxaliplatin, fluorouracil, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with radiation therapy and combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving bevacizumab together with combination chemotherapy after surgery may kill any tumor cells that remain after surgery.
PRIMARY OBJECTIVES: I. To evaluate the pathological complete response rate in patients with T3 and T4 rectal cancers when treated preoperatively with capecitabine, oxaliplatin, bevacizumab, and concurrent radiotherapy (XRT). II. To evaluate the resection rate for T3 and T4 rectal cancers and the expected versus actual type of resection (abdominoperinal resection \[APR\] vs. low anterior resection \[LAR\] vs. LAR/coloanal anastomosis). III. To make preliminary observations of patient survival and patterns of recurrence for this treatment combination. IV. To gain additional experience regarding the toxicity and tolerability of this preoperative and postoperative regimen. OUTLINE: PREOPERATIVE CHEMORADIOTHERAPY: Patients undergo radiotherapy (total dose to the tumor bed was 5040 cGy) once daily (QD) 5 days a week and receive capecitabine 825 mg/m\^2 orally (PO) twice daily (BID) 5 days a week for 5.5 weeks. Patients also receive oxaliplatin 50 mg/m\^2 intravenously (IV) over 2 hours on days 1, 8, 15, 22, and 29 and bevacizumab 5 mg/kg IV over 30-90 minutes on days 1, 15, and 29 during radiotherapy. SURGERY: Approximately 6-8 weeks after completion of chemoradiotherapy, patients undergo surgical resection. Patients whose tumors are not completely resected or who have metastatic disease discontinue protocol therapy. POSTOPERATIVE CHEMOTHERAPY: Approximately 4-12 weeks after surgery, patients receive oxaliplatin IV over 2 hours, leucovorin calcium 400 mg/m\^2 IV over 2 hours, and bevacizumab 5 mg/kg IV over 30-90 minutes on day 1. Patients also receive fluorouracil 2400 mg/m\^2 IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 9 courses in the absence of disease progression or unacceptable toxicity. Patients then receive up to 3 additional courses of leucovorin calcium, fluorouracil, and bevacizumab. After completion of study treatment, patients are followed up periodically for 10 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
57
Given IV
Given PO
Given IV
Given IV
Given IV
Undergo radiotherapy
Undergo surgical resection
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
The Hospital of Central Connecticut
New Britain, Connecticut, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Atlanta VA Medical Center
Decatur, Georgia, United States
Medical Center of Central Georgia
Macon, Georgia, United States
Pathologic Complete Response Rate
Pathologic complete response to preoperative therapy was determined at the time of surgical resection. Pathologic complete response (pCR) is defined as no evidence of invasive cells on pathologic examination of the primary rectal cancer (or tissue from the area where the tumor had been if there is a complete clinical response). Pathologic complete response rate is calculated as number of patients achieving pathologic complete response divided by all eligible and treated patients
Time frame: Assessed at surgery time
Resection Rate for T3 Rectal Cancers
Resection rate is defined as number of patients with T3 rectal cancer who underwent curative surgical resection among all eligible and treated patients with T3 rectal cancers
Time frame: Assessed at surgery time
Resection Rate for T4 Rectal Cancers
Resection rate is defined as number of patients with T4 rectal cancer who underwent curative surgical resection among all eligible and treated patients with T4 rectal cancers
Time frame: Assessed at surgery time
5-year Overall Survival Rate
Overall survival is defined as time from registration to death from any cause. 5-year overall survival rate is estimated using Kaplan-Meier method.
Time frame: survival follow-up began after post-operative chemotherapy, assessed every 3 months for patients 3-5 years from registration, every 6 months for patients 5-10 years from registration and every 12 months for patients 10 years from registration
5-year Recurrence-free Survival Rate
Recurrence free survival is defined as time from surgery to disease recurrence or death without recurrence (whichever occurred first) among resected patients. 5-year recurrence-free survival rate is estimated using Kaplan-Meier method, with 90% confidence interval calculated using Greenwood's formula.
Time frame: recurrence follow-up began after post-operative chemotherapy, assessed every 3 months for patients 3-5 years from registration, every 6 months for patients 5-10 years from registration and every 12 months for patients 10 years from registration
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