Neoadjuvant FOLFOXIRI Versus Immediate Surgery for Stage II and III Colon Cancers
- Conditions
- Colon Cancer Stage IIColon Cancer Stage III
- Interventions
- Drug: neoadjuvant chemotherapyIProcedure: ColectomyDrug: adjuvant chemotherapy
- Registration Number
- NCT05194878
- Lead Sponsor
- Sun Yat-sen University
- Brief Summary
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.
- Detailed Description
This trial is a a two-arm, multicenter, open labelled, prospective, randomized phase III studies. Eligible patients with High-risk Resectable Stage II and III (T4 or T3 with extramural depth≧5 mm) colon cancer patients will be randomly assigned, in a 2:1 ratio, to receive either perioperative or postoperative chemotherapy.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 840
- 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
- Adequate full blood count: WBC >3.0 x109/l; Plts >100 x109/l. Anaemia (Hb < 10.0 g/dl) is not an exclusion, but should be corrected by transfusion prior to surgery and chemotherapy. If Hb remains low despite transfusions, surgery and chemotherapy can be given at the decision of the surgical and oncology teams.
- Adequate renal biochemistry: serum creatinine was less than 1.5 times the normal value.
- Adequate hepatobiliary function: serum total bilirubin and ALT were less than 1.5 times the normal value.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- 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)
- Colonic obstruction that has not been defunctioned
- Serious medical comorbidity, eg uncontrolled inflammatory bowel disease, uncontrolled angina or recent (<6 months) MI
- Another serious medical condition judged to compromise ability to tolerate neoadjuvant therapy and/or surgery
- Any other malignant disease within the preceding 5 years with the exception of non-melanomatous skin cancer, carcinoma in situ and early stage disease with a recurrence risk <5%
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Neoadjuvant chemotherapy neoadjuvant chemotherapyI 12 weeks of FOLFOXIRI neuoadjuvantly followed by surgery and adjuvant chemotherapy Neoadjuvant chemotherapy Colectomy 12 weeks of FOLFOXIRI neuoadjuvantly followed by surgery and adjuvant chemotherapy Postoperative chemotherapy Colectomy surgery followed by 24 weeks of FOLFOX or CapeOX or Cape Postoperative chemotherapy adjuvant chemotherapy surgery followed by 24 weeks of FOLFOX or CapeOX or Cape
- Primary Outcome Measures
Name Time Method Disease-free survival 2 years Defined as the time from randomization to relapse or death, whichever occurred first
- Secondary Outcome Measures
Name Time Method Surgical morbidity 30 days post surgery Complication after surgery
CT staging from randomization to surgery completed, up to 6 months the accuracy of CT staging
Overall survival 5 years Defined as the time from randomization to death from any cause
Down-staging of primary tumors 1 year Down-staging of the resected tumour as measured by histopathological tumour diameter and stage according to the TNM staging system of AJCC (7th version)
Chemotherapy toxicity through chemotherapy administration, up to 6 months The grade of toxicity will be assessed using the NCI common toxicity criteria, version 4.0
R0 resection rate after surgery completed, up to 1 month Quality of resection specimen
CT assessment of response to neoadjuvant treatment up to 6 months CT evaluation of the thickness of tumor walls or tumor diameter or tumor length. Efficacy evaluation will be assessed using the RECIST criteria, version 1.1.
Trial Locations
- Locations (1)
651 Dongfeng Road East
🇨🇳Guangzhou, Guangdong, China