Back to resultsCetuximab+mFOLFOX6 VS. mFOLFOX6 Alone in RAS/BRAF Wild Type Patients With High-Risk Resectable CRLM
Primary Purpose
Colorectal Cancer, Liver Metastases
Status
Not yet recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
mFOLFOX6 + Cetuximab
mFOLFOX 6
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
Eligibility Criteria
Inclusion Criteria: Histological proof of colorectal adenocarcinoma; Age ≥ 18 years and ≤75 years; RAS wild type； CRS≥3； Simultaneous liver-limited metastases; At least one measurable liver metastases; World Health Organization (WHO) performance status 0-1; Life expectancy ≥ 3 months; Adequate hematologic function: absolute neutrophil count (ANC)≥1.5×109/l, platelets≥100×109/l, and hemoglobin(HB) ≥ 9g/dl; Adequate liver and renal function: total bilirubin ≤2.0 mg/dl, serum transaminases ≤ 5x upper limit of normal(ULN), and serum creatinine ≤ 1.5x ULN and creatinine clearance ≥ 30 ml/min; Written informed consent. Exclusion Criteria: Previous systemic treatment for metastatic disease; Previous surgery for metastatic disease; Extrahepatic metastases; Unresectable primary tumor; Major cardiovascular events (myocardial infarction, severe/unstable angina, congestive heart failure, CVA) within 12 months before randomisation; Acute or subacute intestinal obstruction; Second primary malignancy within the past 5 years; Drug or alcohol abuse; No legal capacity or limited legal capacity; Pregnant or lactating women; Uncontrolled hypertension, or unsatisfactory blood pressure control with ≥3 antihypertensive drugs; Peripheral neuropathy;
Sites / Locations
- Zhongshan hosptial, Fudan University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
mFOLFOX6 + Cetuximab
mFOLFOX6
Arm Description
Cetuximab + mFOLFOX6: Cetuximab (500mg/m2 IV ) will be given. Oxaliplatin (85 mg/m2 IV over 2 h on day 1), Leucovorin calcium (350 mg/m2 IV over 2 h on day 1) plus a bolus of 5FU (400 mg/m2) followed by a 46h-48h IV infusion of 5FU 2400 mg/m2 will be repeated for every 2 weeks. The regimens repeat every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
mFOLFOX6: Oxaliplatin (85 mg/m2 IV over 2 h on day 1), Leucovorin calcium (350 mg/m2 IV over 2 h on day 1) plus a bolus of 5FU (400 mg/m2) followed by a 46h-48h IV infusion of 5FU 2400 mg/m2 will be repeated for every 2 weeks. The regimens repeat every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Event-free survival
The Event-free survival (EFS) was defined as the period from the start of initial medication to the date of tumor relapse, progression, or death
Secondary Outcome Measures
overall survival
The overall survival (OS) was defined as the period from the start of initial medication until death from any cause, at which point the data was censored.
postoperative hospital stay
The postoperative hospital stay is defined as the number of date from the first day after operation to discharge.
postoperative complication
Patients will be evaluated for surgical morbidity during 1 month. Postoperative morbidity will be scored according 'Clavien-Dindo Grade'.
postoperative mortality
any death occured within 90 days after the last resection of primary and metastatic lesions
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05948072
Brief Title
Cetuximab+mFOLFOX6 VS. mFOLFOX6 Alone in RAS/BRAF Wild Type Patients With High-Risk Resectable CRLM
Official Title
Pre-and Post-operative Cetuximab Plus mFOLFOX6 Versus mFOLFOX6 Alone in RAS/BRAF Wild Type Patients With High-Risk Resectable Colorectal Liver Metastases
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 15, 2023 (Anticipated)
Primary Completion Date
July 15, 2026 (Anticipated)
Study Completion Date
July 15, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
Brief Summary
For patients with initially resectable colorectal cancer liver metastases who have high-risk factors, neoadjuvant therapy is currently considered a consensus approach. However, there is ongoing debate regarding the optimal treatment strategy. Our study aims to investigate whether the addition of cetuximab to neoadjuvant chemotherapy improves outcomes compared to neoadjuvant chemotherapy alone. The objective of this phase III clinical trial is to determine whether the combination of cetuximab and mFOLFOX6 chemotherapy is superior to neoadjuvant mFOLFOX6 chemotherapy alone for patients with initially resectable colorectal cancer liver metastases who have wild-type RAS/BRAF and high-risk factors.
Detailed Description
Primary
• To determine whether the addition of cetuximab to neoadjuvant mFOLFOX6 chemotherapy results in improved event-free survival when compared with neoadjuvant mFOLFOX6 chemotherapy alone in patients with high-risk & RAS/BRAF-wild-type & resectable colorectal liver metastases.
Secondary
To evaluate the overall survival of patients treated with these regimens.
To evaluate the quality of life of patients treated with these regimens.
To evaluate the preoperative remission rate, safety, surgical complications, actual resection rate, pathological resection status of patients treated with these regimens.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Liver Metastases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
250 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
mFOLFOX6 + Cetuximab
Arm Type
Experimental
Arm Description
Cetuximab + mFOLFOX6: Cetuximab (500mg/m2 IV ) will be given. Oxaliplatin (85 mg/m2 IV over 2 h on day 1), Leucovorin calcium (350 mg/m2 IV over 2 h on day 1) plus a bolus of 5FU (400 mg/m2) followed by a 46h-48h IV infusion of 5FU 2400 mg/m2 will be repeated for every 2 weeks. The regimens repeat every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Arm Title
mFOLFOX6
Arm Type
Active Comparator
Arm Description
mFOLFOX6: Oxaliplatin (85 mg/m2 IV over 2 h on day 1), Leucovorin calcium (350 mg/m2 IV over 2 h on day 1) plus a bolus of 5FU (400 mg/m2) followed by a 46h-48h IV infusion of 5FU 2400 mg/m2 will be repeated for every 2 weeks. The regimens repeat every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
mFOLFOX6 + Cetuximab
Intervention Description
Cetuximab + mFOLFOX6: Cetuximab (500mg/m2 IV ) will be given. Oxaliplatin (85 mg/m2 IV over 2 h on day 1), Leucovorin calcium (350 mg/m2 IV over 2 h on day 1) plus a bolus of 5FU (400 mg/m2) followed by a 46h-48h IV infusion of 5FU 2400 mg/m2 will be repeated for every 2 weeks. The regimens repeat every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
mFOLFOX 6
Intervention Description
mFOLFOX6: Oxaliplatin (85 mg/m2 IV over 2 h on day 1), Leucovorin calcium (350 mg/m2 IV over 2 h on day 1) plus a bolus of 5FU (400 mg/m2) followed by a 46h-48h IV infusion of 5FU 2400 mg/m2 will be repeated for every 2 weeks. The regimens repeat every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Primary Outcome Measure Information:
Title
Event-free survival
Description
The Event-free survival (EFS) was defined as the period from the start of initial medication to the date of tumor relapse, progression, or death
Time Frame
3 years
Secondary Outcome Measure Information:
Title
overall survival
Description
The overall survival (OS) was defined as the period from the start of initial medication until death from any cause, at which point the data was censored.
Time Frame
5 years
Title
postoperative hospital stay
Description
The postoperative hospital stay is defined as the number of date from the first day after operation to discharge.
Time Frame
30 days post operatively
Title
postoperative complication
Description
Patients will be evaluated for surgical morbidity during 1 month. Postoperative morbidity will be scored according 'Clavien-Dindo Grade'.
Time Frame
After surgery during one month
Title
postoperative mortality
Description
any death occured within 90 days after the last resection of primary and metastatic lesions
Time Frame
After surgery during 90 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histological proof of colorectal adenocarcinoma;
Age ≥ 18 years and ≤75 years;
RAS wild type；
CRS≥3；
Simultaneous liver-limited metastases;
At least one measurable liver metastases;
World Health Organization (WHO) performance status 0-1;
Life expectancy ≥ 3 months;
Adequate hematologic function: absolute neutrophil count (ANC)≥1.5×109/l, platelets≥100×109/l, and hemoglobin(HB) ≥ 9g/dl;
Adequate liver and renal function: total bilirubin ≤2.0 mg/dl, serum transaminases ≤ 5x upper limit of normal(ULN), and serum creatinine ≤ 1.5x ULN and creatinine clearance ≥ 30 ml/min;
Written informed consent.
Exclusion Criteria:
Previous systemic treatment for metastatic disease;
Previous surgery for metastatic disease;
Extrahepatic metastases;
Unresectable primary tumor;
Major cardiovascular events (myocardial infarction, severe/unstable angina, congestive heart failure, CVA) within 12 months before randomisation;
Acute or subacute intestinal obstruction;
Second primary malignancy within the past 5 years;
Drug or alcohol abuse;
No legal capacity or limited legal capacity;
Pregnant or lactating women;
Uncontrolled hypertension, or unsatisfactory blood pressure control with ≥3 antihypertensive drugs;
Peripheral neuropathy;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jianmin Xu, MD
Phone
86-021-64041990
Email
xujmin@aliyun.com
First Name & Middle Initial & Last Name or Official Title & Degree
Dexiang Zhu, MD
Phone
86-13636443958
Email
13636443958@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jianmin Xu, MD
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Zhongshan hosptial, Fudan University
City
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianmin Xu, PhD
Phone
+86-13501984869
Email
xujmin@aiiyun.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Cetuximab+mFOLFOX6 VS. mFOLFOX6 Alone in RAS/BRAF Wild Type Patients With High-Risk Resectable CRLM
We'll reach out to this number within 24 hrs