Preoperative radiation and chemotherapy is the standard treatment for local advanced rectal cancer. The addition of oxaliplatin to capecitabine combined with radiotherapy does not improve local control and long-term survival. Most importantly,chemoradiotherapy significantly increased surgical complication and poor long-term quality of life .In the absence of effective measures of predicting chemo-sensitivity, there is considerable risk of using any two-drug regimen for neoadjuvant therapy. Simultaneous use of the three chemotherapeutic drugs may be able to reduce the likelihood of resistance to both dual drug regimen and single drug regimen. The purpose of this study is to compare the efficacy and safety of three chemotherapeutic regimen known as FOLFOXIRI (the drug 5-fluorouracil, oxaliplatin, Irinotecan) with standard radiotherapy combined with capecitabine in neoadjuvant therapy for local advanced rectal cancer. The drugs in the FOLFOXIRI regimen are all FDA(Food and Drug Administration) approved and have been used routinely to treat patients with advanced colorectal cancer.
Outline: This is a multicenter,prospectively,randomized control ,phase III clinical study.Patients are stratified according to the distance from the tumor to the anal margin(≤5cm,\>5cm) and randomized to 1 of 2 treatment regimen.Patients will receive full supportive care while on this study. Objectives: Primary: To compare neoadjuvant chemotherpay of FOLFOXIRI with conventional capecitabine single-agent radiotherapy in local advanced rectal cancer with respect to 3-year disease free survival rate (DFS) . Secondary: 1. To compare postoperative 3-year local recurrence rate, 3-year distance metastasis free survival rate, 3-year overall survival between neoadjuvant FOLFOXIRI with capecitabine single-agent radiotherapy groups. 2. To compare R0 Resection rate and surgical complication between the two groups. 3. To evaluate the tumor regression grade(TRG) between the two groups. 4. To evaluate the adverse event profile and Long term quality of life between the two groups.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
776
Irinotecan165 mg/m2、Oxaliplatin85 mg/m2、Left-calcium leucovorin 200mg/㎡,Intravenous infusion,first day. Then, 5-FU 1600 mg/m2/d×2 continuous intravenous infusion(total 3200 mg/m2,infusion 46 hours)in the next two days. Repeat every 14 days.
XELOX consisting of 130 mg/m2 oxaliplatin administered intravenously on day 1 and 1,000 mg/m2 capecitabine administered orally twice daily on days 1-14 for a 3-week cycle.
Chemotherapy: oral capecitabine(1650 mg/m2)twice daily during radiotherapy without weekend breaks. Radiation: Radiation therapy is administered via intensity-modulated radiation therapy (IMRT) with a linear accelerator, 6MV-X ray. The patients are scheduled to receive a GTV expanding 6mm to form PTV1 and CTV expanding 6mm to form PTV2. The dose of PTV1 is 50Gy/25 times for 35 days and the dose of PTV2 is 45Gy/25 times for 35 days. Patients were treated in consecutive days per week for a total of 5 weeks.
TME operation
chest/ abdominal CT、pelvic nuclear magnetic resonanceimaging、transrectal ultrasonography
Cancer center of Sun Yat-sen University
Guangzhou, Guangdong, China
RECRUITINGMedical Oncology,Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
NOT_YET_RECRUITING3-year disease free survival rate
3-year disease free survival was defined as the interval from randomization to disease local recurrence and distance metastasis, death, or the last follow-up within 3 years. Patients without any event (metastasis or death) at the last follow-up date were regarded as random censoring.
Time frame: up to 5 years
3-year local recurrence rate
3-year disease local recurrence was defined as the interval from randomization to local recurrence, death, or the last follow-up within 3 years. Patients without any event (local recurrence or death) at the last follow-up date were regarded as random censoring.
Time frame: up to 5 years
3-year distance metastasis free survival rate
3-year distance metastasis was defined as the interval from randomization to distance metastasis, death, or the last follow-up within 3 years. Patients without any event (distance metastasis or death) at the last follow-up date were regarded as random censoring.
Time frame: up to 5 years
5-year overall survival rate
5-year overall survival was defined as the interval from the date of randomization until death of any cause or the last follow-up within 5 years.
Time frame: up to 5 years
R0 Resection rate
Percentage of included patients who were performed radical tumor resection among total included patients
Time frame: up to 5 years
Surgical complication
Surgical complication including anastomotic leakage , anastomotic stricture , intestinal obstruction , postoperative pelvic bleeding, and poor wound healing.
Time frame: up to 5 years
Tumor regression grade (TRG)
The tumor regression grade(TRG) were assessed using the Mandard TRG system.
Time frame: up to 5 years
Number of Adverse events
Treatment related adverse events were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (CTCAE4.0)
Time frame: up to 5 years
Long term quality of life
Long term quality of life were assessed by European organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ C30)
Time frame: up to 5 years
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