Neoadjuvant FOLFOXIRI Versus Immediate Surgery for Stage II and III Colon Cancers

NCT05194878 | Recruiting Phase 3

• 1 other identifier: 2021-FXY-244
• Study Type: interventional
• Target: 840
• Locations: 1 country
• Sites: 1

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.

Conditions

Colon Cancer Stage II; Colon Cancer Stage III

Keywords

neoadjuvent chemotherapy; FOLFOXIRI; colon caner

Outcome Measures

Primary Outcomes (1)

• Disease-free survival

  Defined as the time from randomization to relapse or death, whichever occurred first

  2 years

Secondary Outcomes (7)

• Overall survival

  5 years

• Down-staging of primary tumors

  1 year

• Chemotherapy toxicity

  through chemotherapy administration, up to 6 months

• R0 resection rate

  after surgery completed, up to 1 month

• Surgical morbidity

  30 days post surgery

Study Arms (2)

Neoadjuvant chemotherapy

EXPERIMENTAL

12 weeks of FOLFOXIRI neuoadjuvantly followed by surgery and adjuvant chemotherapy

Drug: neoadjuvant chemotherapyI; Procedure: Colectomy

Postoperative chemotherapy

ACTIVE COMPARATOR

surgery followed by 24 weeks of FOLFOX or CapeOX or Cape

Procedure: Colectomy; Drug: adjuvant chemotherapy

Interventions

neoadjuvant chemotherapyI DRUG

mFOLFOXIRI (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.

Also known as: mFOLFOXIR

Neoadjuvant chemotherapy

Colectomy PROCEDURE

Radical colectomy

Neoadjuvant chemotherapy; Postoperative chemotherapy

adjuvant chemotherapy DRUG

mFOLFOX6 (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.

Also known as: FOLFOX/CapeOX/Cape

Postoperative chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.

You may not qualify if:

• 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%

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

651 Dongfeng Road East

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Colectomy; Chemotherapy, Adjuvant; Folfox protocol

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)

Surgical Procedures, Colorectal; Digestive System Surgical Procedures; Surgical Procedures, Operative; Combined Modality Therapy; Therapeutics; Drug Therapy

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

Study Record Dates

• First Submitted: December 21, 2021
• First Posted: January 18, 2022
• Study Start: December 1, 2021
• Primary Completion: December 1, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 18, 2022

Record last verified: 2022-01

Locations

CN (1)