Neoadjuvant Chemoradiotherapy Versus Neoadjuvant Chemotherapy For Unresectable Locally Advanced Colon Cancer

NCT03970694 | Terminated Phase 3 DMC

• 1 other identifier: 2018-FXY-194
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

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. 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. 2.. Main research indicator: 5-year overall survival rate
3. 3.. Secondary research indicators: 1. R0 resection rate 2. 3-year tumor-free survival rate
4. 4.. Research groups assignment: 1. Research group: Neoadjuvant chemoradiotherapy group; 2. Control group: Neoadjuvant chemotherapy group.
5. 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. 6.. Research protocols:

Conditions

Colon Cancer

Keywords

Neoadjuvant chemoradiotherapy; Colon Cancer; Initial Diagnosed Unresectable Locally Advanced Stage; Phase 3 Clinical Trial

Outcome Measures

Primary Outcomes (1)

• 5-year overall survival rate

  The percentage of patients survive 5 years after treatment.

  5 years after treatment

Secondary Outcomes (2)

• R0 resection rate

  an average of 6 to 12 weeks after surgery

• 3-year progression-free survival rate

  3 years after treatment

Study Arms (2)

Neoadjuvant chemoradiotherapy group

EXPERIMENTAL

Neoadjuvant chemoradiotherapy（XELOX \* 4 + radiotherapy）→ Surgery (if possible) → post-surgery chemotherapy.

Radiation: Radiotherapy; Drug: oxaliplatin+capecitabine

Neoadjuvant chemotherapy group

OTHER

Arm Type: control. Neoadjuvant chemotherapy（XELOX \* 4）→ Surgery (if possible) → post-surgery chemotherapy.

Drug: oxaliplatin+capecitabine

Interventions

Radiotherapy RADIATION

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.

Neoadjuvant chemoradiotherapy group

oxaliplatin+capecitabine DRUG

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.

Neoadjuvant chemoradiotherapy group; Neoadjuvant chemotherapy group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Tumor infiltrates through the intestinal wall and adheres to tissues and organs around the colon(T4b), imaging assesses that R0 resection is unachievable.
• Pericolonic lymph node involvement is closely adjacent to the large abdominal vessels, imaging assesses that lymphadenectomy is difficult.
• Surgical exploration indicates that R0 resection is not achievable.
• 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):
• Routine blood test: WBC\>4000/mm3; PLT\>100000/mm3; Hb\>6g/dl.
• Liver function: SGOT, SGPT and Bilirubin are less than or equal to 1.5 times normal upper limit.
• Renal function: Creatinine is less than or equal to 1.5 times normal upper limit.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

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MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Yuan-hong Gao, M.D

  Sun Yat-sen University

  STUDY CHAIR

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

Model Details: Research group: Neoadjuvant chemoradiotherapy group Control group: Neoadjuvant chemotherapy group

Study Record Dates

• First Submitted: May 26, 2019
• First Posted: May 31, 2019
• Study Start: May 11, 2019
• Primary Completion: May 30, 2022
• Study Completion: June 5, 2022
• Last Updated: June 8, 2022

Record last verified: 2022-06

Locations

CN (1)