Modified Sandwich Therapeutic Regimen for Locally Advanced Rectal Cancer

Study Overview
=================
Brief Summary
-----------------
In the treatment of locally advanced rectal cancer, the short-term and long-term efficacy of the traditional sandwich regimen has not reached satisfactory efficacy. For this reason, the concept of reducing the dose of postoperative chemotherapy or directly moving forward the full amount of postoperative chemotherapy was proposed, which is called total neoadjuvant therapy (TNT). However, TNT also includes the high toxicity of oxaliplatin in the whole process and the long time interval between the end of radiotherapy and the operation, which leads to fibrosis of the surrounding tissue, which increases the difficulty of surgical resection and makes it difficult to ensure good surgical specimen quality. In addition to this, there are issues that may increase the risk of potential disease progression in patients with poor treatment withdrawal. Therefore, appropriately reducing the intensity of chemotherapy and controlling the total duration of preoperative neoadjuvant therapy during radiotherapy is expected to alleviate the side effects of neoadjuvant therapy. Here, the investigators synthesized the characteristics of TNT and sandwich regimens and proposed a XELOX regimen and capecitabine alternate administration combined with preoperative intensity modulated radiation therapy.

Official Title
-----------------
Single Arm and Phase II Clinical Trial of a Sandwich Regimen as XELOX Regimen and Capecitabine Alternate Administration Combined With Preoperative Intensity Modulated Radiation Therapy for pMMR Locally Advanced Rectal Cancer

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

Intervention / Treatment
-----------------
* Drug: XELOX
* Drug: Capecitabine monotherapy
* Radiation: Radiation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pathological confirmed rectal adenocarcinoma. Clinical stage T3-4 or T any N1.With or without MRF positivity, with or without EMVI positivity, R0 resection is estimated. No metastasis No signs of intestinal obstruction; or intestinal obstruction has been relieved after proximal colostomy surgery. Age ranged from 18 to 75 No previous radiotherapy，surgery and chemotherapy. Exclusion Criteria: Multiple primary tumor Cachexy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

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

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sandwich Regimen<br>All rectal patients in this group will receive standard surgical resection. | Drug: XELOX<br>* Starting from the first day of radiotherapy (set as day 0), the patient received a total of 4 courses of XELOX chemotherapy on days -42, -21, 42, and 63, including oxaliplatin 130 mg/m2, intravenous administration, d1, repeat every 3 weeks; and capecitabine 1000mg/m2, twice daily, d1-d14, repeat every 3 weeks.<br>Drug: Capecitabine monotherapy<br>* During radiotherapy (Monday to Friday), capecitabine was administered at 1650 mg/m2/d, twice a day.<br>Radiation: Radiation<br>* The TV is expanded by 6-7mm to form PTV1, and the CTV is expanded by 6-7mm to form PTV2. The dose of PTV1 was 50Gy/25 times/35 days, and the dose of PTV2 was 45Gy/25 times/35 days, 5 times/week for a total of 5 weeks.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of pCR | rate of pathological complete remission | One week after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DFS | Disease free survival | 3 years | 
| OS | overall survival | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Rectal cancer, neoadjuvant chemoradiotherapy, optimization