Neoadjuvant FOLFOXIRI Versus Immediate Surgery for Stage II and III Colon Cancers
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-75
SponsorSun Yat-sen University
About this trial
BACKGROUND:
In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant chemotherapy with FOLFOX or CAPOX regimens has become a standard treatment. However, 20 to 30 % of these patients will develop distant metastasis, which ultimately result in death. Perioperative chemotherapy is a promising strategy with potential benefits that could be more effective at eradicating micrometastases. Moreover, shrinking tumor before surgery not only facilitate removal of all the tumor by the surgeon but also reduce tumor cell spreading during the procedure. With recent advances in radiology, preoperative computed tomography allows a good prediction of tumor stage (wall penetration and nodal involvement) prior to surgery. The investigators conducted the present randomized study to explore whether perioperative chemotherapy with FOLFOXIRI regimen compared with postoperative chemotherapy could improve disease-free survival in patients with radiologically staged, High-risk, but resectable Stage II or III colon cancer.
OBJECTIVE:
The primary objective of this study is to evaluate the efficacy of perioperative chemotherapy with FOLFOXIRI regimen compared to postoperative chemotherapy in patients with High-risk Resectable Stage II and III colon cancer. Secondary objectives are efficacy in terms of R0 resection rate, overall survival (OS), relapse-free survival (RFS), down-staging of primary tumors, and tolerability of perioperative therapy and postoperative complications.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically proven adenocarcinoma or high grade dysplasia on histology plus unequivocal radiological evidence of invasive cancer of the colon(≥ 12 cm from the anal verge).
pMMR in immunohistochemical detection or MSI-H in MSI test.
Determined preoperatively by either spiral or multidetector CT: high risk T3 (tumor disruption of muscle wall and extension into pericolic fat with more than 5 mm protrusion into adjacent mesenteric fat) or T4 (tumor penetrates to the surface of the visceral peritoneum or directly invades or is adherent to adjacent organs or structures).
Patients presenting with acute colonic obstruction may enter the trial only after obstruction is relieved by a successful defunctioning stoma, and when recovered to a fitness level consistent with the other eligibility criteria
Disqualifiers
Any patient for whom radiotherapy is advised by the MDT
Strong evidence of distant metastases or peritoneal nodules (M1)
dMMR in immunohistochemical detection or MSI-L/MS-S in MSI test.
Peritonitis (secondary to perforated tumour)
Trial design
Design model
Parallel
Treatments tested in this trial
neoadjuvant chemotherapyI
DrugmFOLFOXIRI (IV oxaliplatin given over 120 min at a dose of 85 mg/m2 on day 1 followed by IV leucovorin 400 mg/m2 over 2h, IV Irinotecan 150 mg/m2 and IV infusional 5-Fluorouracil 2400 mg/m2 over 48h every 14 days) for 6 cycles followed by colectomy (3 to 6 weeks after) . If PD was observed after 3 cycles, direct colectomy was performed.
Colectomy
Procedure/SurgeryRadical colectomy
adjuvant chemotherapy
DrugmFOLFOX6 (IV oxaliplatin given over 120 min at a dose of 85 mg/m2 on day 1 followed by IV leucovorin 400 mg/m2 over 2h, IV bolus 5-Fluorouracil 400 mg/m2 and IV infusional 5-Fluorouracil 2400 mg/m2 over 46h every 14 days) . CAPOX (IV oxaliplatin given over 120 min at a dose of 130 mg/m2 on day 1, oral capecitabine 1000 mg/m2 twice daily on days 1 through 14 every 21 days) . Oral capecitabine 1000 mg/m2 twice daily on days 1 through 14 every 21 days. The plan and cycles are determined according to the surgical pathology and physical conditions.
Treatment groups
840 Participants
are divided into 2 treatment groupsGroup A: Neoadjuvant chemotherapyExperimental treatment 2 interventions
Group B: Postoperative chemotherapyActive comparator 2 interventions
Trial outcomes
Primary outcomes
1
Disease-free survival
Defined as the time from randomization to relapse or death, whichever occurred first
Time frame
2 yearsSecondary outcomes
1
Overall survival
Defined as the time from randomization to death from any cause
Time frame
5 years2
Down-staging of primary tumors
Down-staging of the resected tumour as measured by histopathological tumour diameter and stage according to the TNM staging system of AJCC (7th version)
Time frame
1 year3
Chemotherapy toxicity
The grade of toxicity will be assessed using the NCI common toxicity criteria, version 4.0
Time frame
through chemotherapy administration, up to 6 months4
R0 resection rate
Quality of resection specimen
Time frame
after surgery completed, up to 1 monthSponsors and contacts
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Source ClinicalTrials.gov