Neoadjuvant Chemoradiotherapy Versus Neoadjuvant Chemotherapy For Unresectable Locally Advanced Colon Cancer

June 5, 2022 updated by: Yuan-hong Gao, Sun Yat-sen University

Neoadjuvant Chemoradiotherapy Versus Neoadjuvant Chemotherapy For Unresectable Locally Advanced Colon Cancer: An Open, Multi-centered, Randomize Controlled Phase 3 Trial.

A. Background and purpose:

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for unresectable locally advanced colon cancer: an open, multi-centered, randomize controlled phase 3 trial.

Colorectal cancer is one of the most common malignant tumors, the morbidity and mortality rate are both in rising trend. 10-23% newly diagnosed colon cancer is at locally advanced stage and surgically unresectable. For this subgroup, treatment guidelines recommend neoadjuvant chemotherapy with or without targeted therapy. However, less than 50% patients could convert into R0 resectable, therapeutic effect is unsatisfactory, 5-year overall survival rate is only 12.5%-45.7%.[JCO,2010] Since 2006, neoadjuvant chemoradiotherapy has been a recommendation as standard treatment for locally advanced rectal cancer, and has been widely applied to clinical use. As for locally advanced colon cancer, it still lacks evidence to support whether neoadjuvant chemoradiotherapy is a beneficial option. There are only several articles about locally advanced colon cancer undertaking neoadjuvant chemoradiotherapy before surgery through Pubmed research, including 3 case reports, 1 abstract and 5 clinical researches with a small sample size, 3 of which are from the investigator's study group.

The investigators recently reported clinical data about therapeutic effect of 60 unresectable locally advanced colon cancer cases and the results were exciting. According to the results, through neoadjuvant chemoradiotherapy, R0 resection rate is 86%, local recurrence rate is 10.2%, 3-year OS and 5-year OS are 76.7% and 66.6%, respectively. [Onco Targets Ther, 2018] "Colorectal cancer diagnoses and treatment guidelines" written by Chinses Society of Clinical Oncology (ver. 2017, 2018), suggested that neoadjuvant chemoradiotherapy was an optional treatment strategy or secondary recommended treatment strategy. In a word, the investigators' result was referred as revisory basis of the guideline [CJC,2016], with a relatively low level of evidence in evidence-based medicine.

This phase 3 clinical trial mainly aims to acquire a higher level of evidence in evidence-based medicine on the subject about neoadjuvant chemoradiotherapy as a treatment strategy to unresectable locally advanced colon cancer, and the ultimate goal is to rewrite the International treatment guidelines of locally advanced colorectal cancer.

B. Research Content:

  1. . Research Object: Patients who newly diagnosed unresectable locally advanced colon cancer. Including: 1. tumor infiltrates through the intestinal wall and adheres to tissues and organs around the colon(T4b), imaging assesses that R0 resection is unachievable. 2. Pericolonic lymph node involvement is closely adjacent to the large abdominal vessels, imaging assesses that lymphadenectomy is difficult. 3. Surgical exploration indicates that R0 resection is not achievable. 4. In initial diagnosis, surgeon evaluates the need for extensive multi-organ combined resection and expected to damage the organs, which would seriously affect the postoperative quality of life.
  2. . Main research indicator: 5-year overall survival rate
  3. . Secondary research indicators: 1. R0 resection rate 2. 3-year tumor-free survival rate
  4. . Research groups assignment: 1. Research group: Neoadjuvant chemoradiotherapy group; 2. Control group: Neoadjuvant chemotherapy group.
  5. . Sample calculation: Calculation is based on the main research indicator: 5-year survival rate. Based on α=0.05(bilateral), β=0.20(unilateral), 5-year OS improves from 45% in control group to 65% in research group, 4-year period, 5-year follow-up. Research group and control group should at least enroll 74 and 75 qualified cases, respectively, a total of 149 cases, with an expected delisting rate of 20%, the total sample size is 186, 93 cases for each group.
  6. . Research protocols:

1. Research group: Neoadjuvant chemoradiotherapy（XELOX * 4 + radiotherapy）→ Surgery (if possible) → post-surgery chemotherapy.

2. Control group: Neoadjuvant chemotherapy（XELOX * 4）→ Surgery (if possible) → post-surgery chemotherapy.

Chemotherapy strategy: XELOX: oxaliplatin 130mg/m2, iv drip, d1, every 3 weeks; capecitabine 1,000mg/m2, bid, d1-d14, every 3 weeks. Concurrent chemotherapy: mXELOX: which oxaliplatin is 100mg/m2.

Radiotherapy strategy: IMRT, 6-8MV X-ray; GTV 45-50Gy/25F, 1.8-2.0Gy/F; CTV 42.5-45Gy/25F, 1.7-1.8Gy/F; Actual delivery dose should be adjusted according to max tolerance dose of organs at risk, but the delivery dose of GTV and CTV must within the required range.

Surgery: Reexamination is performed 5 weeks after radiotherapy for research group and 2 weeks after the fourth period of chemotherapy, surgery is performed in 6-12 weeks after neoadjuvant treatment.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 3

Contacts and Locations

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

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Sun Yat-Sen University Cancer Center

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 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histology confirms colonic adenocarcinoma.
  • The distance from the lower edge of the tumor to the anal edge is greater than or equal to 15cm (from sigmoid colon to ileocecal region)

  • Preoperative staging (Satisfying any one out of four conditions below)

    1. Tumor infiltrates through the intestinal wall and adheres to tissues and organs around the colon(T4b), imaging assesses that R0 resection is unachievable.
    2. Pericolonic lymph node involvement is closely adjacent to the large abdominal vessels, imaging assesses that lymphadenectomy is difficult.
    3. Surgical exploration indicates that R0 resection is not achievable.
    4. In initial diagnosis, surgeon evaluates the need for extensive multi-organ combined resection and expected to damage the organs, which would seriously affect the postoperative quality of life.
  • No obvious signs of intestinal obstruction, or obstruction has been relieved after proximal enterostomy.
  • Preoperative CT/MRI/PET-CT has ruled out distant metastasis.

  • Blood and biochemical indexes achieve standard (Satisfying all three conditions below):

    1. Routine blood test: WBC>4000/mm3; PLT>100000/mm3; Hb>6g/dl.
    2. Liver function: SGOT, SGPT and Bilirubin are less than or equal to 1.5 times normal upper limit.
    3. Renal function: Creatinine is less than or equal to 1.5 times normal upper limit.

Exclusion Criteria:

  • History: Has colon surgery history; Received chemotherapy or biotherapy in the past 5 years; Received radiotherapy in treatment field.
  • Infectious disease: HIV infection history; Active phase chronic hepatitis B or hepatitis C (high copies of virus DNA); Other serious active clinical infection.
  • Diagnosed as stage I colon cancer.
  • Extraperitoneal distant metastasis is positive in pre-operative stage.
  • Dyscrasia or organ decompensation.
  • Received radiation therapy in abdominal or pelvic regions.
  • Multiple primary cancer.
  • Epileptic seizures requiring medical treatment.
  • Other malignant tumor history in the past 5 years (except endocervical cancer in situ or skin basal cell carcinoma which had been cured)
  • Chronic inflammatory colorectal disease, unrelieved ileus.
  • Drug abuse, has medical, psychological or social condition that might affect research results.
  • Allergic to research-related drugs.
  • Any unstable situation that might endanger patient's safety or compliance.
  • Pregnant, lactating woman patient or fertile but lacks adequate contraceptives.
  • Refuses to sign informed consent.

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
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Neoadjuvant chemoradiotherapy group
Neoadjuvant chemoradiotherapy（XELOX * 4 + radiotherapy）→ Surgery (if possible) → post-surgery chemotherapy.
Radiation: Radiotherapy
Since 2006, neoadjuvant chemoradiotherapy has been a recommendation as standard treatment for locally advanced rectal cancer, and has been widely applied to clinical use. As for locally advanced colon cancer, it still lacks evidence to support whether neoadjuvant chemoradiotherapy is a beneficial option.We recently reported clinical data about therapeutic effect of 60 unresectable locally advanced colon cancer cases and it was exciting. According to our results, through neoadjuvant chemoradiotherapy, R0 resection rate is 86%, local recurrence rate is 10.2%, 3-year OS and 5-year OS are 76.7% and 66.6%, respectively."Colorectal cancer diagnoses and treatment guidelines" written by Chinses Society of Clinical Oncology (ver. 2017, 2018), suggested that neoadjuvant chemoradiotherapy was an optional treatment strategy or secondary recommended treatment strategy.
Drug: oxaliplatin+capecitabine
Colorectal cancer is one of the most common malignant tumors, the morbidity and mortality rate are both in rising trend. 10-23% newly diagnosed colon cancer is at locally advanced stage and surgical unresectable. For this subgroup, treatment guidelines recommend neoadjuvant chemotherapy with or without targeted therapy.
OTHER: Neoadjuvant chemotherapy group
Arm Type: control. Neoadjuvant chemotherapy（XELOX * 4）→ Surgery (if possible) → post-surgery chemotherapy.
Drug: oxaliplatin+capecitabine
Colorectal cancer is one of the most common malignant tumors, the morbidity and mortality rate are both in rising trend. 10-23% newly diagnosed colon cancer is at locally advanced stage and surgical unresectable. For this subgroup, treatment guidelines recommend neoadjuvant chemotherapy with or without targeted therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
5-year overall survival rate
Time Frame: 5 years after treatment
The percentage of patients survive 5 years after treatment.
5 years after treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
R0 resection rate
Time Frame: an average of 6 to 12 weeks after surgery
The percentage of patients whose post-operative pathology indicate negative margin is observed under microscope
an average of 6 to 12 weeks after surgery
3-year progression-free survival rate
Time Frame: 3 years after treatment
The percentage of patients have no tumor progression after treatment.
3 years after treatment

Collaborators and Investigators

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

Sponsor

Sun Yat-sen University

Collaborators

First Affiliated Hospital, Sun Yat-Sen University
Tongji Hospital
Second Affiliated Hospital, School of Medicine, Zhejiang University
Nanfang Hospital of Southern Medical University
Sixth Affiliated Hospital, Sun Yat-sen University
Fujian Medical University Union Hospital

Investigators

  • Study Chair: Yuan-hong Gao, M.D, Sun Yat-sen University

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)

May 11, 2019

Primary Completion (ACTUAL)

May 30, 2022

Study Completion (ACTUAL)

June 5, 2022

Study Registration Dates

First Submitted

May 26, 2019

First Submitted That Met QC Criteria

May 30, 2019

First Posted (ACTUAL)

May 31, 2019

Study Record Updates

Last Update Posted (ACTUAL)

June 8, 2022

Last Update Submitted That Met QC Criteria

June 5, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018-FXY-194

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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