Bevacizumab, Radiation Therapy, and Combination Chemotherapy in Treating Patients Who Are Undergoing Surgery for Locally Advanced Nonmetastatic Rectal Cancer
This phase II trial is studying how well giving bevacizumab together with 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.
Adenocarcinoma of the Rectum
Stage II Rectal Cancer
Stage III Rectal Cancer
Radiation: 3-dimensional conformal radiation therapy
Procedure: therapeutic conventional surgery
Drug: leucovorin calcium
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Preoperative Radiation With Concurrent Capecitabine, Oxaliplatin and Bevacizumab Followed by Surgery and Postoperative 5-FU, Leucovorin, Oxaliplatin (FOLFOX) and Bevacizumab in Patients With Locally Advanced Rectal Cancer|
- Pathological complete response rate [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]A two-stage design will be used and 90% confidence intervals will be provided.
- Grade 3 or higher toxicities according to NCI CTCAE v3.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]A two-stage monitoring plan will be used and 90% confidence intervals will be provided.
- Resection rate [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]There will be 82% power to detect a 45% absolute difference in resection rate between 95% in T3 rectal cancer patients and 50% in T4 rectal cancer patients at significance level of 0.10 using Fisher's exact test. The expected versus actual types of resection (APR or LAR or LAR/coloanal anastomosis) will be summarized and reported in an exploratory fashion.
- Overall survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]Will be estimated using Kaplan-Meier method.
- Time to recurrence [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]Will be estimated using Kaplan-Meier method. The patterns of recurrence in terms of timing of recurrence and locations of recurrence will be explored and summarized.
|Study Start Date:||July 2006|
|Primary Completion Date:||March 2011 (Final data collection date for primary outcome measure)|
Experimental: Arm I
See detailed description.
Radiation: 3-dimensional conformal radiation therapy
Other Names:Drug: capecitabine
Other Names:Drug: oxaliplatin
Other Names:Biological: bevacizumab
Other Names:Procedure: therapeutic conventional surgery
Undergo surgical resectionDrug: leucovorin calcium
Other Names:Drug: fluorouracil
I. Evaluate the pathological complete response rate in patients with T3 or T4 rectal cancer treated with neoadjuvant bevacizumab in combination with radiotherapy, capecitabine, and oxaliplatin followed by surgical resection and adjuvant bevacizumab in combination with fluorouracil, leucovorin calcium, and oxaliplatin.
I. Evaluate the resection rate for T3 and T4 rectal cancers. II. Evaluate the expected versus actual type of resection (abdominoperineal resection [APR] vs low anterior resection [LAR] vs LAR/coloanal anastomosis) performed on these patients.
III. Determine, preliminarily, survival and patterns of recurrence in patients treated with this regimen.
IV. Determine the toxicity and tolerability of this preoperative and postoperative regimen.
OUTLINE: This is a multicenter study. Patients are stratified according to primary tumor size (T3 vs T4).
PREOPERATIVE CHEMORADIOTHERAPY: Patients undergo radiotherapy once daily 5 days a week and receive oral capecitabine twice daily 5 days a week for 5.5 weeks. Patients also receive oxaliplatin IV over 2 hours on days 1, 8, 15, 22, and 29 and bevacizumab 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 4-8 weeks after surgery, patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV over 30-90 minutes on day 1. Patients also receive fluorouracil (5-FU) 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, 5-FU, and bevacizumab.
After completion of study treatment, patients are followed periodically for 10 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00321685
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|Principal Investigator:||Jerome Landry||Eastern Cooperative Oncology Group|