Effect of Concurrent Capecitabine-based Long-term Radiotherapy Followed by XELOX Plus TME in Patients With High Risk Rectal Cancer: a Multi-centers, Randomized Controlled, Open-Label Trial (EXPLORE)

March 19, 2023 updated by: YE Yingjiang, Peking University People's Hospital

Effect of Concurrent Capecitabine-based Long-term Radiotherapy Followed by 4 Cycles XELOX Pre- a Delayed TME Compared With 6 Cycles XELOX post-a Regular Timing TME in Patients With High Risk Rectal Cancer: a Multi-centers, Randomized, Open-Label Trial

The purpose of this study was to evaluate the effect of concurrent capecitabine-based long-term radiotherapy followed by 4 cycles XELOX pre- a delayed TME compared with 6 cycles XELOX post- a Regular Timing TME in patients with high-risk rectal cancer defined by MRI.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is the randomized controlled, multi-centers, and open-labeled study. Delivering systemic chemotherapy between concurrent capecitabine-based long-term radiotherapy and total mesorectal excision (TME) surgery would be more effectively improved local control rates and improved metastases-free survival rates. The investigators attempted to investigate the effect on pathological response of delivering 4 cycles XELOX between concurrent capecitabine-based long-term radiotherapy and TME with lengthening the interval from radiation to surgery. In this study, the participants with high risk of deeper infiltration, or extramural vessel invasion, or circumferential resection margin involvement, or surrounding organs and structures invaded et al. were recruited. The participants will be randomized (1:1 ratio) to a control and intervention arm. The participants in the control arm will receive best current practice of concurrent capecitabine-based long-term radiotherapy followed by TME and then a 6 cycles of XELOX as standard adjuvant chemotherapy. The participants in the intervention arm will receive concurrent capecitabine-based long-term radiotherapy followed by 4 cycles XELOX as neoadjuvant chemotherapy pre- a delayed TME.

Study Type

Interventional

Enrollment (Anticipated)

244

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100044
        • Recruiting
        • Peking University People's Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Yingjiang Ye, M.D./PhD
      • Beijing, Beijing, China
        • Not yet recruiting
        • Beijing Friendship Hospital
        • Contact:
          • Zhongtao Zhang, professor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age of 18-75 years;
  2. Histologically confirmed adenocarcinoma;
  3. The rectal adenocarcinoma 0-12cm from the anal margin on Magnetic resonance imaging (MRI) and/or rigid sigmoidoscopy;
  4. High risk of rectal cancer defined by high-resolution MRI: tumor invasion 5mm beyond the muscularis propria, or extramural vascular invasion, or circumferential resection margin unsafe, or the lower rectal cancer invades intersphincteric space, or rectal cancer invades the adjacent structures.
  5. Eastern Collaborative Oncology Group performance status score of 0 or 2
  6. Able and willing to give informed consent to participate.

Exclusion Criteria:

  1. Received preoperative chemoradiotherapy for rectal cancer before the recruitment of this study;
  2. Have metastatic disease (including non-regional lymph nodes metastases or resectable liver metastases);
  3. Other malignancies, non-adenocarcinoma rectal malignancies or rectal malignancies on the basis of inflammatory bowel disease;
  4. Emergency surgery due to bowel obstruction, perforation, bleeding, etc.;
  5. Abnormality of capecitabine absorption due to gastrointestinal disease e.g. short bowel syndrome, inflammation bowel disease, et al.;
  6. Unresectable concurrent intestinal lesions;
  7. Concurrent severe infection；
  8. Cardiac Disease：uncontrolled or symptomatic cardiac angina，or uncontrolled arrhythmias and hypertension, or severe congestive heart failure grade II or more based on New York Heart Association (NYHA); myocardial infarction within the past 12 months
  9. Peripheral neuropathy more than grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE; version 3·0)
  10. Bone marrow, liver and kidney function are abnormal e.g., white blood cell ≤ 1.5 × 109 / L; platelet ≤ 100 × 109 / L; Haemoglobin ≤ 80 g/L; Bilirubin > 1.5 times the upper limit; aspartate aminotransferase and alanine aminotransferase > 2.5 times the upper limit; creatinine > 1.5 times the upper limit;
  11. Pregnant or lactating women;
  12. Life prediction less than 3 months, other severe diseases;
  13. Contraindication to MRI; e.g. non-MRI compatible hip prosthesis, cardiac pacemaker;
  14. Contraindication to standard chemotherapy including drug interactions and glomerular filtration rate <50 mL/min at baseline;
  15. Participators who had been recruited by other clinical trial within three months.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 4 Cycles XELOX pre- TME
experimental group (arm B): concurrent capecitabine-based long-term radiotherapy, 4 cycles of XELOX as neoadjuvant chemotherapy and TME surgery
Drug: concurrent capecitabine-based long-term radiotherapy followed by 4 cycles XELOX and a delayed TME

concurrent capecitabine-based long-term radiotherapy: capecitabine 825mg/m2,bid,d1-5, q week with Radiation treatment. Radiation treatment was given at 1·8 Gy per day, 5 days per week for 5-6 weeks, after a 45 Gy radiation dose in 25 fractions to the pelvis, a boost dose of 5·4 Gy in 3 fractions to the tumor bed or concurrent boosted.

XELOX:

Oxaliplatin: 130mg/m2,IV,d1; Capecitabine: 1000mg/m2,bid,d1-14; repeated every 3 weeks

Surgery Procedure:

Total Mesorectal Excision
Active Comparator: 6 Cycles XELOX post- TME
control group (arm A): concurrent capecitabine-based long-term radiotherapy, TME surgery and 6 cycles of XELOX as adjuvant chemotherapy.
Drug: concurrent capecitabine-based long-term radiotherapy followed by a Regular TME and 6 Cycles XELOX

concurrent capecitabine-based long-term radiotherapy: capecitabine 825mg/m2,bid,d1-5, q week with Radiation treatment. Radiation treatment was given at 1·8 Gy per day, 5 days per week for 5-6 weeks, after a 45 Gy radiation dose in 25 fractions to the pelvis, a boost dose of 5·4 Gy in 3 fractions to the tumor bed or concurrent boosted.

XELOX:

Oxaliplatin: 130mg/m2,IV,d1; Capecitabine: 1000mg/m2,bid,d1-14; repeated every 3 weeks

Surgery Procedure:

Total Mesorectal Excision

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological complete response rate
Time Frame: up to 30days after total mesorectal excision
Pathological complete response (pCR) rate between control and intervention arm
up to 30days after total mesorectal excision

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Surgery morbidity
Time Frame: 30 days and 12-months
Surgical morbidity reported according to Clavien-Dindo classification
30 days and 12-months
Disease Free Survival
Time Frame: 3-year
Disease Free Survival was defined as the time from the date of surgery to the date of the local recurrence, and/or distant disease, or tumor-related death.
3-year
R0 of total mesorectal excision rate
Time Frame: up to 30days after total mesorectal excision
Overall R0 of total mesorectal excision rate between the control and intervention arm
up to 30days after total mesorectal excision
quality of surgery
Time Frame: Time of surgery
Quality of surgery determined using the mesorectal grading system
Time of surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University People's Hospital

Collaborators

Xijing Hospital
Beijing Friendship Hospital
Peking Union Medical College Hospital
Shanghai Zhongshan Hospital
Chinese PLA General Hospital
Peking University Cancer Hospital & Institute
Nanfang Hospital of Southern Medical University
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Affiliated Hospital of Hebei University
Fujian Medical University Union Hospital
Hebei Medical University Fourth Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 31, 2018

Primary Completion (Anticipated)

April 1, 2023

Study Completion (Anticipated)

June 1, 2025

Study Registration Dates

First Submitted

January 25, 2017

First Submitted That Met QC Criteria

January 28, 2017

First Posted (Estimate)

January 31, 2017

Study Record Updates

Last Update Posted (Actual)

March 22, 2023

Last Update Submitted That Met QC Criteria

March 19, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-12 EXPLORE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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