This phase II trial studies how well bevacizumab, fluorouracil, leucovorin calcium, and oxaliplatin before surgery works in treating patients with stage II-III rectal cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as fluorouracil, leucovorin calcium, and oxaliplatin, 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 fluorouracil, leucovorin calcium, and oxaliplatin may be an effective treatment for rectal cancer.
PRIMARY OBJECTIVES: I. To determine if six cycles of modified fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX7) plus bevacizumab (Avastin) will yield complete pathologic response (cPR) of 25% or more in the primary tumor of patients with stage II and III rectal cancer. SECONDARY OBJECTIVES: I. To assess the rate of tumor regression (pathologic stage lower than clinical stage) after 6 cycles of mFOLFOX7 and bevacizumab in the primary rectal cancer. II. To assess local recurrence rate over 3 years after 6 cycles of mFOLFOX7 and bevacizumab. TERTIARY OBJECTIVES: I. Correlation of the following marker with response (defined as CPR or down staging): * Intratumoral Gene expression and germline polymorphism of genes involved in the vascular endothelial growth factor (VEGF) and VEGF independent pathways (VEGF, vascular endothelial growth factor receptor 1 \[VEGFR1\], VEGFR2, interleukin-8 \[IL8\], chemokine (C-X-C motif) receptor 2 \[CXCR2\], intercellular adhesion molecule \[ICAM\], VEGFR1 and VEGFR2, neuropilin 1 or 2 \[NRP1,2\], cluster of differentiation \[CD\] 44, aldehyde dehydrogenase \[ALDH\], leucine-rich repeats and immunoglobulin-like \[LRIG\]. * Circulating tumor cells (CTC) and VEGF-factor A (A) on the CTC. II. Prediction of surgical resection margin by pretreatment magnetic resonance imaging (MRI). OUTLINE: Patients receive bevacizumab intravenously (IV) over 30-90 minutes, oxaliplatin IV over 2 hours, leucovorin calcium IV, and fluorouracil IV continuously over 46-48 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Within 6-8 weeks after treatment, patients undergo surgery. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
17
Given IV
Given IV
Given IV
Given IV
Correlative studies
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States
Number of Participants With Pathological Complete Response (pCR) to Neoadjuvant Therapy
Pathological Complete Response (pCR) after neoadjuvant therapy in pathological specimen. Pathological Complete Response (pCR) is the absence of all invasive cancer in the breast and lymph nodes after neoadjuvant therapy, meaning all cancer cells are eliminated. This outcome is a strong predictor of improved survival. Evaluating pCR provides a rapid assessment of a patient's likely response to therapy and can help guide future treatment decisions.
Time frame: Up to 3 years
Tumor Regression on Mesorectal Margins (Pathologic Stage Lower Than Clinical Stage)
Time frame: Up to 3 years
Rate of Locoregional Recurrence
Number of cancer patients who experience a return of their cancer in the original tumor site or in the nearby lymph nodes following initial treatment. It is a measure of how often cancer returns to the local area where it started, rather than spreading to distant organs.
Time frame: Up to 3 years
Number of Participants With Adverse Events (AEs)
Incidence and nature of adverse events (AEs) according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 ( v4)
Time frame: Up to 3 years
Number of Participants With Serious AEs (SAEs) According to NCI CTCAE v4.0
Time frame: Up to 3 years
Number of Participants of AEs of Special Interest for Bevacizumab (Grades) According to NCI CTCAE v4.0
Time frame: Up to 3 years
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