Neoadjuvant Chemoradiotherapy Versus Neoadjuvant Chemotherapy For Unresectable Locally Advanced Colon Cancer
Status:
Recruiting
Trial end date:
2028-12-01
Target enrollment:
Participant gender:
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:
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.
Phase:
Phase 3
Details
Lead Sponsor:
Sun Yat-sen University
Collaborators:
First Affiliated Hospital, Sun Yat-Sen University Fujian Medical University Union Hospital Nanfang Hospital of Southern Medical University Second Affiliated Hospital, School of Medicine, Zhejiang University Sixth Affiliated Hospital, Sun Yat-sen University Tongji Hospital