Cetuximab+mFOLFOX6 VS. mFOLFOX6 Alone in RAS/BRAF Wild Type Patients With High-Risk Resectable CRLM

NCT ID: NCT05948072

Last Updated: 2023-07-17

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-15
• Study Completion Date: 2026-07-15

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.

Conditions

Colorectal Cancer; Liver Metastases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

mFOLFOX6 + Cetuximab

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.

Group Type: EXPERIMENTAL

mFOLFOX6 + Cetuximab

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

mFOLFOX 6

Intervention Type: DRUG

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.

Interventions

mFOLFOX6 + Cetuximab

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

mFOLFOX 6

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

Eligibility Criteria

Inclusion Criteria

1. Histological proof of colorectal adenocarcinoma;

2. Age ≥ 18 years and ≤75 years;

3. RAS wild type；

4. CRS≥3；

5. Simultaneous liver-limited metastases;

6. At least one measurable liver metastases;

7. World Health Organization (WHO) performance status 0-1;

8. Life expectancy ≥ 3 months;

9. Adequate hematologic function: absolute neutrophil count (ANC)≥1.5×109/l, platelets≥100×109/l, and hemoglobin(HB) ≥ 9g/dl;

10. 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;

11. Written informed consent.

Exclusion Criteria

1. Previous systemic treatment for metastatic disease;

2. Previous surgery for metastatic disease;

3. Extrahepatic metastases;

4. Unresectable primary tumor;

5. Major cardiovascular events (myocardial infarction, severe/unstable angina, congestive heart failure, CVA) within 12 months before randomisation;

6. Acute or subacute intestinal obstruction;

7. Second primary malignancy within the past 5 years;

8. Drug or alcohol abuse;

9. No legal capacity or limited legal capacity;

10. Pregnant or lactating women;

11. Uncontrolled hypertension, or unsatisfactory blood pressure control with ≥3 antihypertensive drugs;

12. Peripheral neuropathy;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Xu jianmin

Director of the Department of Colorectal Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jianmin Xu, MD

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Zhongshan hosptial, Fudan University

Shanghai, , China

Countries

China

Central Contacts

Jianmin Xu, MD

Role: CONTACT

xujmin@aliyun.com

86-021-64041990

Dexiang Zhu, MD

Role: CONTACT

13636443958@163.com

86-13636443958

Facility Contacts

Jianmin Xu, PhD

Role: primary

xujmin@aiiyun.com

+86-13501984869

Other Identifiers

NEO-HR-CRLM

Identifier Type: -

Identifier Source: org_study_id