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

Primary Purpose

Colon Cancer Stage II, Colon Cancer Stage III

Status

Recruiting

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

neoadjuvant chemotherapyI

Colectomy

adjuvant chemotherapy

About this trial

This is an interventional treatment trial for Colon Cancer Stage II focused on measuring neoadjuvent chemotherapy, FOLFOXIRI, colon caner

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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%

Sites / Locations

651 Dongfeng Road EastRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Neoadjuvant chemotherapy

Postoperative chemotherapy

Arm Description

12 weeks of FOLFOXIRI neuoadjuvantly followed by surgery and adjuvant chemotherapy

surgery followed by 24 weeks of FOLFOX or CapeOX or Cape

Outcomes

Primary Outcome Measures

Disease-free survival

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

Secondary Outcome Measures

Overall survival

Defined as the time from randomization to death from any cause

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)

Chemotherapy toxicity

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

R0 resection rate

Quality of resection specimen

Surgical morbidity

Complication after surgery

CT staging

the accuracy of CT staging

CT assessment of response to neoadjuvant treatment

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.

Full Information

NCT ID

NCT05194878

First Posted

December 21, 2021

Last Updated

January 14, 2022

Sponsor

Sun Yat-sen University

1. Study Identification

Unique Protocol Identification Number

NCT05194878

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2022

Overall Recruitment Status

Recruiting

Study Start Date

December 1, 2021 (Actual)

Primary Completion Date

December 2024 (Anticipated)

Study Completion Date

December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colon Cancer Stage II, Colon Cancer Stage III

Keywords

neoadjuvent chemotherapy, FOLFOXIRI, colon caner

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

840 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Neoadjuvant chemotherapy

Arm Type

Experimental

Arm Description

12 weeks of FOLFOXIRI neuoadjuvantly followed by surgery and adjuvant chemotherapy

Arm Title

Postoperative chemotherapy

Arm Type

Active Comparator

Arm Description

surgery followed by 24 weeks of FOLFOX or CapeOX or Cape

Intervention Type

Drug

Intervention Name(s)

neoadjuvant chemotherapyI

Other Intervention Name(s)

mFOLFOXIR

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

Colectomy

Intervention Description

Radical colectomy

Intervention Type

Drug

Intervention Name(s)

adjuvant chemotherapy

Other Intervention Name(s)

FOLFOX/CapeOX/Cape

Intervention Description

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.

Primary Outcome Measure Information:

Title

Disease-free survival

Description

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

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Overall survival

Description

Defined as the time from randomization to death from any cause

Time Frame

5 years

Title

Down-staging of primary tumors

Description

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 year

Title

Chemotherapy toxicity

Description

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

Time Frame

through chemotherapy administration, up to 6 months

Title

R0 resection rate

Description

Quality of resection specimen

Time Frame

after surgery completed, up to 1 month

Title

Surgical morbidity

Description

Complication after surgery

Time Frame

30 days post surgery

Title

CT staging

Description

the accuracy of CT staging

Time Frame

from randomization to surgery completed, up to 6 months

Title

CT assessment of response to neoadjuvant treatment

Description

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.

Time Frame

up to 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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%

Facility Information:

Facility Name

651 Dongfeng Road East

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Peirong Ding, Doctor

Phone

13543478645

Ext

+86

dingpr@sysucc.org.cn

First Name & Middle Initial & Last Name & Degree

Yuan Li, Doctor

Phone

18816800377

Ext

+86

liyuan@sysucc.org.cn

12. IPD Sharing Statement

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

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