Randomized Trial of Primary Surgery Followed Selective Radiochemotherapy for Rectal Cancer With MRI Negative CRM

Phase 3

Suspended

• Conditions: Colorectal Neoplasm; Effects of Radiation Therapy; Effects of Chemotherapy; Surgery
• Interventions: Procedure: Rectectomy; Radiation: Radiotherapy; Drug: Capecitabine; Drug: Oxaliplatin

• Registration Number: NCT02121405
• Lead Sponsor: Zhejiang University

Brief Summary

The purpose of this study is to determine whether primary radiotherapy can be omitted for the locally advanced rectal cancer with Magnetic Resonance Imaging (MRI) negative circumferential margin.

Detailed Description

The preoperative radiochemotherapy with fluorouracil followed surgery is the standard therapy for patients with locally advanced rectal cancer. However, the necessity of radiotherapy has been questioned for a long time especially for patients with enough circumferential margins. Moreover, indiscriminate radiotherapy will result Irreversible ovarian dysfunction for female. In the past decade, there were two major progresses for colorectal cancer. Firstly, oxaliplatin with fluorouracil has become the standard adjuvant chemotherapy for advanced colon cancer. Oxaliplatin improved the survival of colon cancer patients than single fluorouracil. Our experience showed that oxaliplatin with fluorouracil could improve the prognosis of rectal cancer without radiotherapy. It has been proven that oxaliplatin should not add to radiotherapy for rectal cancer. However, whether oxaliplatin can replace radiotherapy for certain rectal cancer patients is still unknown. Secondly, Magnetic Resonance Imaging (MRI) has been proven that can predict the circumferential margin status for rectal cancer. Now, preoperative MRI scan can recognize the rectal cancer patients with low recurrence risk. The radiotherapy may be omitted to the patients with low recurrence risk. This study is a randomized controlled trial to compare the 3-year disease-free survival (DFS) differences of group of experiment (the patients receive primary surgery followed selective radiochemotherapy) and group of control (the patients receive indiscriminate preoperative radiochemotherapy followed surgery) for locally advanced rectal cancer with negative MRI circumferential margin.

Study Timeline

• Study First Submitted: 2014-04-21
• Study First Submitted QC: 2014-04-22
• Study First Posted: 2014-04-23
• Study Start: 2015-10
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-05
• Last Update Posted: 2022-05-11
• Primary Completion: 2024-02
• Study Completion: 2026-02

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 350

Inclusion Criteria

• Rectal adenocarcinoma or mucinous adenocarcinoma that is 6-12 cm from the anal verge.
• MRI scan confirmed cT3N0 or cT4aN0 or cT1-4aN+ mid rectal cancer (6-12cm from the anal verge).
• MRI scan confirmed more than 1 mm circumferential margin.
• Age 18-75 years old.
• Without distant metastasis.

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Exclusion Criteria

• Malignant history.
• Contraindications of MRI scan.
• Contraindications of radiotherapy.
• Contraindications of chemotherapy.
• Pregnancy.
• Multidisciplinary team thinks that the patient is unsuitable to take part in research (For example, there are obvious regional lymph nodes involved in low rectal cancer patients who are thought with high risk of recurrence).
• Refuse to take part in research.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Preoperative radiochemotherapy	Rectectomy	All of the patients receive conventional concurrent radiochemotherapy with capecitabine for 5 weeks. Then all of the patients receive 2 cycles/6 weeks capecitabine ± Oxaliplatin chemotherapy. Patients receive rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with total mesorectal excision 8 weeks post radiotherapy. All of the patients receive 5 cycles/15 weeks capecitabine ± Oxaliplatin adjuvant chemotherapy. The use of Oxaliplatin depends on the doctor's decision.
Preoperative radiochemotherapy	Radiotherapy	All of the patients receive conventional concurrent radiochemotherapy with capecitabine for 5 weeks. Then all of the patients receive 2 cycles/6 weeks capecitabine ± Oxaliplatin chemotherapy. Patients receive rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with total mesorectal excision 8 weeks post radiotherapy. All of the patients receive 5 cycles/15 weeks capecitabine ± Oxaliplatin adjuvant chemotherapy. The use of Oxaliplatin depends on the doctor's decision.
Primary surgery	Rectectomy	The patients receive primary rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with TME. To patients with pathological confirmed positive circumferential margin (CRM), postoperative concurrent radiochemotherapy is required that starts in 3 months post operation with capecitabine. Capecitabine and Oxaliplatin (CapeOx) chemotherapy starts in 4 weeks post operation to total of 6 cycles/18 weeks. To patients with pathological confirmed negative CRM, radiotherapy is omitted. The stage III patients receive 8 cycles/6 months CapeOx chemotherapy. The stage II patients with low microsatellite instability (MSI) receive 8 cycles/6 months Capecitabine chemotherapy. The stage II patients with high MSI and stage I patients do not receive adjuvant therapy.
Primary surgery	Radiotherapy	The patients receive primary rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with TME. To patients with pathological confirmed positive circumferential margin (CRM), postoperative concurrent radiochemotherapy is required that starts in 3 months post operation with capecitabine. Capecitabine and Oxaliplatin (CapeOx) chemotherapy starts in 4 weeks post operation to total of 6 cycles/18 weeks. To patients with pathological confirmed negative CRM, radiotherapy is omitted. The stage III patients receive 8 cycles/6 months CapeOx chemotherapy. The stage II patients with low microsatellite instability (MSI) receive 8 cycles/6 months Capecitabine chemotherapy. The stage II patients with high MSI and stage I patients do not receive adjuvant therapy.
Primary surgery	Oxaliplatin	The patients receive primary rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with TME. To patients with pathological confirmed positive circumferential margin (CRM), postoperative concurrent radiochemotherapy is required that starts in 3 months post operation with capecitabine. Capecitabine and Oxaliplatin (CapeOx) chemotherapy starts in 4 weeks post operation to total of 6 cycles/18 weeks. To patients with pathological confirmed negative CRM, radiotherapy is omitted. The stage III patients receive 8 cycles/6 months CapeOx chemotherapy. The stage II patients with low microsatellite instability (MSI) receive 8 cycles/6 months Capecitabine chemotherapy. The stage II patients with high MSI and stage I patients do not receive adjuvant therapy.
Primary surgery	Capecitabine	The patients receive primary rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with TME. To patients with pathological confirmed positive circumferential margin (CRM), postoperative concurrent radiochemotherapy is required that starts in 3 months post operation with capecitabine. Capecitabine and Oxaliplatin (CapeOx) chemotherapy starts in 4 weeks post operation to total of 6 cycles/18 weeks. To patients with pathological confirmed negative CRM, radiotherapy is omitted. The stage III patients receive 8 cycles/6 months CapeOx chemotherapy. The stage II patients with low microsatellite instability (MSI) receive 8 cycles/6 months Capecitabine chemotherapy. The stage II patients with high MSI and stage I patients do not receive adjuvant therapy.
Preoperative radiochemotherapy	Oxaliplatin	All of the patients receive conventional concurrent radiochemotherapy with capecitabine for 5 weeks. Then all of the patients receive 2 cycles/6 weeks capecitabine ± Oxaliplatin chemotherapy. Patients receive rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with total mesorectal excision 8 weeks post radiotherapy. All of the patients receive 5 cycles/15 weeks capecitabine ± Oxaliplatin adjuvant chemotherapy. The use of Oxaliplatin depends on the doctor's decision.
Preoperative radiochemotherapy	Capecitabine	All of the patients receive conventional concurrent radiochemotherapy with capecitabine for 5 weeks. Then all of the patients receive 2 cycles/6 weeks capecitabine ± Oxaliplatin chemotherapy. Patients receive rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with total mesorectal excision 8 weeks post radiotherapy. All of the patients receive 5 cycles/15 weeks capecitabine ± Oxaliplatin adjuvant chemotherapy. The use of Oxaliplatin depends on the doctor's decision.

Primary Outcome Measures

Name	Time	Method
Disease-free survival	Three years from the date of randomization

Secondary Outcome Measures

Name	Time	Method
Overall survival	Five years from the date of randomization
Quality of life by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C(core) 30 and QLQ-CR(colorectal) 29 forms	Baseline before any treatment,3 months post operation, 1 year post operation
The rate of positive circumferential resection margin	1 day of postoperative pathological examination.

Trial Locations

Locations (7)

Union Hospital Fujian Medical University; 🇨🇳 Fuzhou, Fujian, China

Zhongshan Hospital Fudan University; 🇨🇳 Shanghai, Shanghai, China

Liaoning Cancer Hospital; 🇨🇳 Shenyang, Liaoning, China

Jinhua People's Hospital; 🇨🇳 Jinhua, Zhejiang, China

Yuyao People's Hospital; 🇨🇳 Yuyao, Zhejiang, China

The First Affiliated Hospital of College of Medicine Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China