Induction Chemotherapy,Radiochemotherapy, Consolidation Chemotherapy in Preoperative Treatment of Rectal Cancer

Study Overview
=================
Brief Summary
-----------------
The use of capecitabine based preoperative chemoradiation and adjuvant chemotherapy is standard treatment of locally advanced rectal cancer. It has reduced local recurrence rate to less than 10%, but has only had limited effect on overall survival due to the constantly high (more than 30%) rate of distant metastasis. Complete eradication of the primary tumour observed in the histopathological specimen (pathological complete response, pCR) correlates with a favourable overall prognosis so obtaining a pCR might be beneficial. The aim of the study is to investigate whether the addition of capecitabine based chemotherapy before preoperative chemoradiation and also before the operation improves pathological complete remission rate in locally advanced rectal cancer with acceptable toxicity. Secondary objectives are to evaluate pathological downstaging rate, histopathological R0 resection rate,sphincter preservation rate, perioperative surgical complication rate, local control, DFS, OS, late toxicity and quality of life.

Official Title
-----------------
Induction Chemotherapy, Preoperative Radiochemotherapy, Consolidation Chemotherapy, Operation and Adjuvant Chemotherapy in the Treatment of Locally Advanced Rectal Cancer- OIGIT 5-01 Phase II Trial

Conditions
-----------------
Rectal Cancer

Intervention / Treatment
-----------------
* Drug: intensified preoperative chemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patients with histologically proven adenocarcinoma of the rectum (tumour located below the peritoneum), T3/4 or any node positive disease (clinical stage according the TNM classification system) No evidence of metastatic disease. The disease must be considered either resectable at the time of entry or thought to become resectable after preoperative chemoradiation. Age 18 years and more WHO Performance Status 0-2 No prior radiotherapy, chemotherapy or any targeting therapy for rectal cancer Adequate hematological, hepatic and renal function Ability to swallow tablets Signed informed consent Patients must be willing and able to comply with the protocol for duration of the study Exclusion Criteria: Malignancy of the rectum other than adenocarcinoma Any unrested synchronous colon cancer Other co-existing malignancy or malignancy within the past 5 years, with the exception of adequately treated in situ carcinoma of the cervix or basal cell carcinoma of the skin Significant heart disease (uncontrolled hypertension despite of medication (> 150/100 mmHg), NYHA class III or IV heart disease,unstable angina or myocardial infarction within the past 1 year prior the study entry, history of significant ventricular arrhythmia requiring treatment) Pregnant or lactating patient Females with a positive or no pregnancy test unless childbearing potential can be otherwise excluded (amenorrheic for at least 2 years,hysterectomy or oophorectomy)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: intensified preoperative chemotherapy|capecitabine 1250 mg/m² p.o. twice daily for 14 consecutive days, 7 days rest for one cycle; radiotherapy: 50.4 Gy to the pelvis (25x 1.8 Gy on days 1-33, excluding weekends) plus 5.4 Gy on days 36-38 as a boost to the primary tumour (3 fractions of 1.8 Gy).Three- dimensional CT planing and a four field box technique with high energy photons (15 MV) will be used. capecitabine 825 mg/m² p.o. twice daily on days 1-38 (including weekends), One week after completion of radiochemotherapy patients receive 2 cycles of capecitabine based chemotherapy (1250 mg/m² p.o. twice daily for 14 consecutive days every three weeks). Radical surgery (TME): to be undertaken 8 weeks following completion of chemoradiation Postoperative treatment:capecitabine 1250 mg/m² p.o. twice daily for 14 consecutive days every three weeks; 3 cycles (R0 beginning 6-8 weeks after surgery|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete remission rate (pCR) |  | after the pathological examination of surgical speciments ie within 14 days after the operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity | Number of patients with adverse events and the grade of adverse events | According to NCI-CTC (version 3.0): every week for 16 week preoperative, perioperative (0-30 days postoperative), early (30 days - 6 months postoperative), and late (more than 6 months postoperative) | 
| Histopathological R0 resection rate |  | after the pathological examination of resected speciments ie within 14 days after the operation | 
| Loco-regional failure rate |  | after 3y and 5y of operation | 
| Disease-free survival |  | after 3y and 5y of operation | 
| Overall survival |  | after 3y and 5y of the operation | 
| Quality of life | We will use EORTC questionnaires QLQ C30 and C38 | before the treatment, after 1,and 3 years of the operation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
rectal cancer, capecitabine, radiotherapy, locally advanced rectal cancer