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

NCT02121405 | Suspended Phase 3 DMC

• 1 other identifier: CRCCZ-R01
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 7

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.

Conditions

Colorectal Neoplasm; Effects of Radiation Therapy; Effects of Chemotherapy; Surgery

Outcome Measures

Primary Outcomes (1)

• Disease-free survival

  Three years from the date of randomization

Secondary Outcomes (3)

• The rate of positive circumferential resection margin

  1 day of postoperative pathological examination.

• 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

• Overall survival

  Five years from the date of randomization

Study Arms (2)

Primary surgery

EXPERIMENTAL

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.

Procedure: Rectectomy; Radiation: Radiotherapy; Drug: Capecitabine; Drug: Oxaliplatin

Preoperative radiochemotherapy

ACTIVE COMPARATOR

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.

Procedure: Rectectomy; Radiation: Radiotherapy; Drug: Capecitabine; Drug: Oxaliplatin

Interventions

Rectectomy PROCEDURE

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

Preoperative radiochemotherapy; Primary surgery

Radiotherapy RADIATION

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.

Preoperative radiochemotherapy; Primary surgery

Capecitabine DRUG

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.

Also known as: Xeloda

Preoperative radiochemotherapy; Primary surgery

Oxaliplatin DRUG

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.

Also known as: Eloxatin

Preoperative radiochemotherapy; Primary surgery

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zhejiang University: lead

Study Sites (7)

Union Hospital Fujian Medical University

Fuzhou, Fujian, 350001, China

Location

Liaoning Cancer Hospital

Shenyang, Liaoning, 110042, China

Location

Zhongshan Hospital Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

The First Affiliated Hospital of College of Medicine Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310016, China

Location

Jinhua People's Hospital

Jinhua, Zhejiang, 321000, China

Location

Yuyao People's Hospital

Yuyao, Zhejiang, 315400, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Radiation Injuries

Interventions

Radiotherapy; Capecitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Therapeutics; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Officials

• Ke-Feng Ding, M.D.

  The Second Affiliated Hospital Zhejiang University Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 21, 2014
• First Posted: April 23, 2014
• Study Start: October 1, 2015
• Primary Completion: February 1, 2024
• Study Completion: February 1, 2026
• Last Updated: May 11, 2022

Record last verified: 2022-05

Locations

CN (7)