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NCT Number: NCT05194878

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

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.

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Key information

Conditions

Colon Cancer Stage II Colon Cancer Stage III Colonic Diseases Colonic Neoplasms Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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%

Treatment and study plan

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.

Other names: mFOLFOXIR

Colectomy

Procedure

Radical colectomy

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.

Other names: FOLFOX/CapeOX/Cape

Primary outcomes

  1. Disease-free survival

    Time frame: 2 years

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

Secondary outcomes

  1. Overall survival

    Time frame: 5 years

    Defined as the time from randomization to death from any cause

  2. Down-staging of primary tumors

    Time frame: 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)

  3. Chemotherapy toxicity

    Time frame: through chemotherapy administration, up to 6 months

    The grade of toxicity will be assessed using the NCI common toxicity criteria, version 4.0

  4. R0 resection rate

    Time frame: after surgery completed, up to 1 month

    Quality of resection specimen

  5. Surgical morbidity

    Time frame: 30 days post surgery

    Complication after surgery

  6. CT staging

    Time frame: from randomization to surgery completed, up to 6 months

    the accuracy of CT staging

  7. CT assessment of response to neoadjuvant treatment

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Sun Yat-sen University

Other

Registry information

Official study title

Phase III Study of Neoadjuvant FOLFOXIRI Chemotherapy Versus Immediate Surgery for High-risk Resectable Stage II and III Colon Cancers

Important dates

Study start
2021
Primary completion
2024
Study completion
2026
First posted
Jan 18, 2022
Registry last updated
Jan 18, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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