Neoadjuvant FOLFOXIRI Versus CapeOX Chemotherapy for Local Advanced Rectal Cancer

Recruitment & Eligibility

Inclusion Criteria

MRI evaluated of T3-4 or N+ rectal cancer;
Pathologically diagnosed of rectal adenocarcinoma;
18 to 75 years old;
Distance from lower margin of tumor to anus <15 cm and suitable for anus-preserving resection;
Tumor amenable to radical resection;
Treatment-na?ve patients with no previous systemic chemotherapy, radiotherapy or local excision for treating rectal cancer;
Laboratory requirements conducted within 7 days of starting study treatment: Neutrophil count ≥ 1.5×10^9/L, Platelet count ≥ 100×10^9 /L, Hemoglobin ≥ 80 g/L, Serum bilirubin ≤ 24umol/L, Alanine aminotransferase and aspartate aminotransferase ≤ 60 U/L, Serum creatinine ≤ 110 umol/L;
Be capable to receive a surgery;
No second tumor at present or in the past 5 years, except skin basal cell carcinoma, skin squamous cell carcinoma, or any in situ cancer;
No previous systemic chemotherapy for treating colorectal cancer;
Life expectancy of more than 3 months;
No current pregnancy or breast-feeding, and subjects at childbearing age shall take method of contraception;
Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1;
Be willing and able to understand the study and to provide written informed consent.

Exclusion Criteria

End-stage cachexia patients;
Cardiopulmonary dysfunction or liver and kidney dysfunction, and unable to tolerate chemotherapy or surgery;
Metastatic carcinoma;
Incomplete or complete intestinal obstruction;
Known to be allergic to capecitabine, 5-Fu, oxaliplatin or irinotecan;
Pregnant or lactating women; or women who have fertility but have not taken at taken adequate contraceptive measures;
Have vital organ failure or other severe diseases, including but not limited to coronary heart disease, cardiovascular diseases, or myocardial infarction within 12 months before being included; severe neurological or psychiatric historysevere infection; active disseminated intravascular coagulation; active hepatitis, severe coagulation disorder patients;
History of other malignancy within the past 5 years except effectively treated skin basal cell carcinoma, skin squamous cell carcinoma, or any in situ cancer;
Serious organic disease including but not limited to heart, kidney, brain, and lung.

Study & Design

Arm && Interventions

Group	Intervention	Description
A: FOLFOXIRI	FOLFOXIRI	Neoadjuvant chemotherapy with 3-4 cycles of FOLFOXIRI regimen, followed by surgery
B: CapeOX	CapeOX	Neoadjuvant chemotherapy with 2-3 cycles of CapeOX regimen, followed by surgery

Primary Outcome Measures

Name	Time	Method
3-year disease free survival	3 years	Defined as the length of time from the date of randomization until the first documented date of progression or death from any cause, whichever comes first. Compare 3-year disease free survival in patients with locally advanced rectal cancer treated with either FOLFOXIRI or CapeOX neoadjuvant chemotherapy.

Secondary Outcome Measures

Name	Time	Method
pathologic complete response rate	1 year	Defined as the ratio of patients with pathologic TRG 0
quality of life as assessed by EORTC QOL-CR29	3 years	Quality of life after neoadjuvant chemotherapy is assessed by questionaires EORTC QOL-CR29.
major pathologic response rate	1 year	Defined as the ratio of patients with pathologic TRG 0 or 1
adverse event	1 year	Number of patients with adverse events and severity according to NCI CTC 5.0 after neoadjuvant chemotherapy.
objective response rate	1 year	Defined as the ratio of patients with MRI-TRG 1, 2 or 3
local recurrence rate	3 years	Defined as the ratio of patients with local recurrence within 3 years.
overall survival	5 years	Defined as the length of time from randomization date until the date of death from any cause.
quality of life as assessed by EORTC QOL-C30	3 years	Quality of life after neoadjuvant chemotherapy is assessed by questionaires EORTC QOL-C30 version 3

Recruitment & Eligibility