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

Surgery Clinical Trial

— PSSR  

Official title:

Randomized Trial of Primary Surgery Followed Selective Radiochemotherapy Versus Conventional Preoperative Radiochemotherapy for Locally Advanced Rectal Cancer With MRI Negative Circumferential Margin

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT02121405
• Other study ID #: CRCCZ-R01
• Status: Suspended
• Phase: Phase 3
• Start date: October 2015
• Est. completion date: February 2026

Study information

• Verified date: May 2022
• Source: Zhejiang University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 350
• Est. completion date: February 2026
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

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.

Related Conditions & MeSH terms

• Colorectal Neoplasm
• Colorectal Neoplasms
• Effects of Chemotherapy
• Effects of Radiation Therapy
• Surgery

Intervention

Procedure:
• Rectectomy
Include anterior resection or abdominoperineal resection by open or laparoscopy with Total Mesorectal Excision (TME).

Radiation:
• Radiotherapy
45-50 Gy in 25-28 fractions to the pelvis. After 45 Gy a tumor bed boost with a 2 cm margin of 5.4 Gy in 3 fractions for preoperative cancers or 5.4-9.0 Gy in 3-5 fractions for postoperative cancers could be considered. Radiotherapy is used only for patients with pathological confirmed positive circumferential margin in Group primary surgery. Radiotherapy is used to all of the patients in Group preoperative radiochemotherapy.

Drug:
• Capecitabine
Capecitabine 825 mg/m2 twice daily 5 or 7 days/week with concurrent radiotherapy in Group primary surgery and Group preoperative radiochemotherapy. Capecitabine 1250 mg/m2 twice daily 1-14 every 3 weeks to a total of 6 weeks after preoperative radiochemotherapy in Group preoperative radiochemotherapy. Capecitabine 1250 mg/m2 twice daily 1-14 every 3 weeks to a total of 6 months postoperative therapy for a part of stage II patients in Group of primary surgery. Capecitabine 1000 mg/m2 twice daily 1-14 every 3 weeks with oxaliplatin day 1 to a total of 6 months postoperative therapy for stage III patients in Group of primary surgery.
• Oxaliplatin
Oxaliplatin 130 mg/m2 over 2 hours, day 1, with capecitabine every 3 weeks. Repeat every 3 weeks to total of 6 months postoperative therapy.

Locations

Country	Name	City	State
China	Union Hospital Fujian Medical University	Fuzhou	Fujian
China	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The First Affiliated Hospital of College of Medicine Zhejiang University	Hangzhou	Zhejiang
China	Jinhua People's Hospital	Jinhua	Zhejiang
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai
China	Liaoning Cancer Hospital	Shenyang	Liaoning
China	Yuyao People's Hospital	Yuyao	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival		Three years from the date of randomization
Secondary	The rate of positive circumferential resection margin		1 day of postoperative pathological examination.
Secondary	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
Secondary	Overall survival		Five years from the date of randomization