Neoadjuvant Chemoradiotherapy Versus Neoadjuvant Chemotherapy For Unresectable Locally Advanced Colon Cancer

Sponsor
Sun Yat-sen University (Other)
Overall Status
Terminated
CT.gov ID
NCT03970694
Collaborator
First Affiliated Hospital, Sun Yat-Sen University (Other), Sixth Affiliated Hospital, Sun Yat-sen University (Other), Fujian Medical University Union Hospital (Other), Second Affiliated Hospital, School of Medicine, Zhejiang University (Other), Nanfang Hospital of Southern Medical University (Other), Tongji Hospital (Other)
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Study Details

Study Description

Brief Summary

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:

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

  8. 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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
49 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Research group: Neoadjuvant chemoradiotherapy group Control group: Neoadjuvant chemotherapy groupResearch group: Neoadjuvant chemoradiotherapy group Control group: Neoadjuvant chemotherapy group
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Neoadjuvant Chemoradiotherapy Versus Neoadjuvant Chemotherapy For Unresectable Locally Advanced Colon Cancer: An Open, Multi-centered, Randomize Controlled Phase 3 Trial.
Actual Study Start Date :
May 11, 2019
Actual Primary Completion Date :
May 30, 2022
Actual Study Completion Date :
Jun 5, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. 5-year overall survival rate [5 years after treatment]

    The percentage of patients survive 5 years after treatment.

Secondary Outcome Measures

  1. R0 resection rate [an average of 6 to 12 weeks after surgery]

    The percentage of patients whose post-operative pathology indicate negative margin is observed under microscope

  2. 3-year progression-free survival rate [3 years after treatment]

    The percentage of patients have no tumor progression after treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Sun Yat-sen University Cancer Center Guangzhou Guangdong China 510060

Sponsors and Collaborators

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

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Yuan-hong Gao, Professor, Sun Yat-sen University
ClinicalTrials.gov Identifier:
NCT03970694
Other Study ID Numbers:
  • 2018-FXY-194
First Posted:
May 31, 2019
Last Update Posted:
Jun 8, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
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
Keywords provided by Yuan-hong Gao, Professor, Sun Yat-sen University
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 8, 2022