Trial Title:
FOLFOX Via HAI Plus Intravenous Irinotecan With or Without Bevacizumab Versus Systemic FOLFOXIRI With or Without Bevacizumab in Initially Unresectable RAS-mutated CRLM Patients
NCT ID:
NCT05727163
Condition:
Colorectal Cancer Metastatic
Conditions: Official terms:
Colorectal Neoplasms
Leucovorin
Dexamethasone
Anisodamine
Bevacizumab
Oxaliplatin
Fluorouracil
Irinotecan
Levoleucovorin
Conditions: Keywords:
Colorectal liver metastasis
Hepatic Artery Infusion Chemotherapy
RAS-mutation
Systemic Chemotherapy
FOLFOX
FOLFOXIRI
Initially unresectable colon cancer
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
25mg via HAI (Pre-chemotherapy)
Arm group label:
HAI group
Intervention type:
Drug
Intervention name:
Anisodamine
Description:
10 mg via HAI (Pre-chemotherapy)
Arm group label:
HAI group
Other name:
654-2
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
85 mg/m2 via HAI over 3 hours
Arm group label:
HAI group
Intervention type:
Drug
Intervention name:
Leucovorin
Description:
200 mg/m2 via HAI
Arm group label:
HAI group
Intervention type:
Drug
Intervention name:
Fluorouracil
Description:
400 mg/m2 via HAI and 2.4g/m2 via HAI over 48 hours
Arm group label:
HAI group
Other name:
FU
Intervention type:
Drug
Intervention name:
Irinotecan
Description:
150 mg/m2 intravenously
Arm group label:
HAI group
Arm group label:
Systemic Chemotherapy group
Intervention type:
Drug
Intervention name:
Bevacizumab
Description:
5 mg/kg intravenously
Arm group label:
HAI group
Arm group label:
Systemic Chemotherapy group
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
85 mg/m2 intravenously over 3 hours
Arm group label:
Systemic Chemotherapy group
Intervention type:
Drug
Intervention name:
Leucovorin
Description:
200 mg/m2 intravenously
Arm group label:
Systemic Chemotherapy group
Intervention type:
Drug
Intervention name:
Fluorouracil
Description:
400 mg/m2 intravenously + 2400 mg/m2 continuous intravenous infusion over 46 hours
Arm group label:
Systemic Chemotherapy group
Other name:
FU
Summary:
This prospective, randomized, controlled clinical study aims to evaluate the objective
remission rate of FOLFOX hepatic artery infusion chemotherapy (HAI) in combination with
systemic irinotecan with or without bevacizumab versus systemic intravenous FOLFOXIRI
with or without bevacizumab in initially unresectable RAS-mutated colorectal cancer
patients with liver metastases.
Detailed description:
PRIMARY OBJECTIVES:
The goal of this prospective, randomized, controlled clinical trial is to evaluate the
objective remission rate (ORR) of FOLFOX hepatic artery infusion chemotherapy (HAI) in
combination with irinotecan with or without bevacizumab systemic intravenous chemotherapy
versus systemic intravenous FOLFOXIRI with or without bevacizumab in initially
unresectable RAS-mutated colorectal cancer patients with liver metastases.
SECONDARY OBJECTIVES:
To assess and compare the depth of response (DpR), R0 surgical resection rate, No
evidence of disease (NED) rate, progression-free survival (PFS), overall survival (OS),
recurrence-free survival (RFS) in resectable patients and safety (chemotherapy-related
adverse events, catheterization-related adverse events, surgical complications, etc.)
between the two intervention groups.
OUTLINE:
Patients in the HAI group receive FOLFOX via hepatic artery infusion chemotherapy plus
intravenous irinotecan with or without bevacizumab every 14 days, while patients in the
systemic group receive intravenous FOLFOXIRI regimen with or without bevacizumab every 14
days. Patients will receive a maximum of 12 cycles in total (before and after surgery)
unless there is disease progression, unacceptable toxicity, or if the patient withdraws
from the study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histologically confirmed colorectal adenocarcinoma
2. Imaging or pathological confirmation of liver metastases
3. The multidisciplinary team determined that the liver metastases were unresectable,
defined as (i) ≥5 metastases; (ii) inability to perform R0 resection; (iii)
insufficient volume of liver expected to remain after resection; (iv) failure to
preserve all 3 hepatic veins after resection, failure to ensure that blood flow to
and from the liver and bile ducts can be preserved, and failure to preserve 2
adjacent liver segments. If any of the above criteria are met, it can be considered
as initially unresectable liver metastases.
4. Patients with mutated RAS and BrafV600E
5. No previous treatment for liver metastases, including chemotherapy, surgery,
radiotherapy, transarterial chemoembolization (TACE) and targeted therapy
6. No extrahepatic metastases confirmed by CT, MRI, or PET/CT (if necessary) (consider
enrollment if there is a lung or lymph node lesion less than 10 mm and metastases
are difficult to identify)
7. Normal hematological function (platelets >90×109/L; white blood cells >3×109/L;
neutrophils >1.5×109/L)
8. Serum bilirubin ≤ 1.5 times the upper limit of normal value (ULN), transaminases ≤ 5
times ULN
9. No ascites, normal coagulation function, albumin ≥35g/L
10. Liver function Child-Push grade A
11. Serum creatinine less than upper limit of normal (ULN) or calculated creatinine
clearance >50 ml/min (using Cockcroft-Gault formula)
12. ECOG score 0-1
13. Life expectancy > 3 months
14. Signed written informed consent
Exclusion Criteria (Patients meeting any of the following criteria will be excluded from
the study):
1. Presence of any extrahepatic metastases and/or primary tumor not amenable to radical
surgical resection
2. Development of liver metastases within 1 year after completion of adjuvant
chemotherapy with FOLFOX or XELOX
3. Severe arterial embolism or ascites
4. Bleeding tendency or coagulation disorder
5. Hypertensive crisis or hypertensive encephalopathy
6. Severe uncontrolled systemic complications such as infections or diabetes mellitus
7. Clinically significant cardiovascular disease such as cerebrovascular accident
(within 6 months prior to enrollment), myocardial infarction (within 6 months prior
to enrollment), uncontrolled hypertension despite appropriate medication, unstable
angina pectoris, congestive heart failure (NYHA class 2-4), arrhythmias requiring
medication
8. History or physical examination revealing a central nervous system disease (e.g.,
primary brain tumor, epilepsy not manageable by standard therapy, presence of brain
metastases, or history of stroke)
9. Previous malignancy within the last 5 years (except post-radical surgery basal cell
carcinoma of the skin and/or carcinoma in situ of the cervix)
10. Treatment using any investigational drug within the last 28 days prior to the study
11. Any residual toxicity from prior chemotherapy (except alopecia), such as peripheral
neuropathy ≥ NCI CTC v3.0 grade 2, will not be considered for treatment with
oxaliplatin-containing regimens
12. History of allergy to any of the drugs in the study
13. Women of childbearing potential (<2 years after last menstruation) or men of
childbearing potential who are not using or have refused to use an effective
non-hormonal contraceptive (IUD, barrier method combined with spermicidal gel or
sterilization) during pregnancy and lactation
14. Unable or unwilling to comply with the study protocol
15. Presence of any other disease, dysfunction due to metastatic lesions, or suspicious
medical findings that suggest a possible contraindication to the use of the study
drug or that would place the patient at risk of treatment-related complications
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Status:
Recruiting
Contact:
Last name:
Yuhong Li, MD
Phone:
020-87342487
Phone ext:
+86
Email:
liyh@sysucc.org.cn
Start date:
July 29, 2022
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05727163
