Conversion Therapy of RAS/BRAF Wild-Type Colorectal Cancer Patients With Initially Unresectable Liver Metastases
Primary Purpose
Colorectal Cancer, Liver Metastases
Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
mFOLFOXIRI plus Cetuximab
mFOLFOXIRI Plus Bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring Cetuximab, Bevacizumab, Triplet Chemotherapeutic Regimen, Colorectal Cancer, Liver Metastases
Eligibility Criteria
Inclusion Criteria:
- The primary tumor was confirmed by histology as colorectal adenocarcinoma
- Initially unresectable liver metastases suggested by MDT
- RAS/BRAF gene wild-type states
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy ≥ 3 months
- Good hematological function: neutrophil ≥ 1.5x109 / L and platelet count ≥ 100x109 / L; HB ≥ 9g / dl (within one week before randomization)
- Normal liver and kidney function: serum bilirubin ≤ 1.5x normal upper limit (ULN), alkaline phosphatase ≤ 5x ULN, serum transaminase (AST or ALT) ≤ 5x ULN (within one week before randomization);
- Sign the written informed consent to participate in the experiment
Exclusion Criteria:
- Patients with liver metastases from colorectal cancer who have previously received targeted therapy, chemotherapy, radiotherapy or interventional therapy
- Known or suspected extrahepatic metastasis
- Patients with known hypersensitivity to any component of the study treatment
- Clinical related coronary heart disease or history of myocardial infarction in the last 12 months or left ventricular ejection fraction below normal range
- Acute or subacute intestinal obstruction
- Pregnancy (no pregnancy confirmed by serum / urine β - hCG) or breastfeeding.
- Other malignant tumors within 5 years, except for those with skin basal cell carcinoma or cervical cancer
- Known drug / alcohol abuse
- No legal capacity or limited legal capacity
Sites / Locations
- Zhongshan Hospital, Fudan UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
mFOLFOXIRI plus Cetuximab
mFOLFOXIRI plus Bevacizumab
Arm Description
Outcomes
Primary Outcome Measures
Conversion resection rate of liver metastases
Rate of conversion from initially unresectable liver metastases to resectable ones
Secondary Outcome Measures
Objective Response Rate
rate of objective response for therapy
Incidence of adverse events
Incidence of adverse events
Progression-Free Survival
Progression free survival
Overall Survival
overall survival
Early tumor shrinkage
The rates of tumor shrinkage by RECIST at 8 weeks
Best deepness of response
the maximum tumor shrinkage rates by RECIST during the treatment of the study
time interval from chemotherapy to hepatectomy
Time interval from the beginning of treatment to hepatectomy
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04687631
Brief Title
Conversion Therapy of RAS/BRAF Wild-Type Colorectal Cancer Patients With Initially Unresectable Liver Metastases
Official Title
Conversion Therapy of RAS/BRAF Wild-Type Colorectal Cancer Patients With Initially Unresectable Liver Metastases: mFOLFOXIRI Plus Cetuximab Versus mFOLFOXIRI Plus Bevacizumab
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 14, 2021 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 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
5. Study Description
Brief Summary
Evidence suggests that the addition of cetuximab or bevacizumab to doublet regimens could improve response rate and resectability rate of liver metastases and survival in colorectal liver metastases (CRLM). Moreover, it is observed that FOLFOXIRI yields higher response and resection rates compared with doublet regimens. However, which is better in conversion therapy of RAS/BRAF wild-type initially unresectable CRLM, FOLFOXIRI plus cetuximab or bevacizumab, remains unknown.
In this study, RAS/BRAF wild-type colorectal cancer patients with initially unresectable liver-only metastases, as prospectively confirmed by a local multidisciplinary team (MDT) according to predefined criteria, will be randomised between modified FOLFOXIRI (mFOLFOXIRI) plus cetuximab and mFOLFOXIRI plus bevacizumab. Patient imaging will be reviewed for resectability by MDT, consisting of at least one radiologist and three liver surgeons every assessment. MDT review will be performed prior to randomization as well as during treatment, as described in the protocol.
Detailed Description
Patients will be stratified for primary tumor location (right-sided or left sided) and numbers of liver metastases (<5 or ≥5).
Patients with RAS mutated primary tumors will be randomized between mFOLFOXIRI plus cetuximab (cetuximab 500 mg/m^2 in 60 minutes i.v., followed by oxaliplatin 85 mg/m^2 i.v. in 120 minutes, followed by irinotecan 165 mg/m^2 i.v. in 60 minutes, together with leucovorin 400 mg/m^2 i.v. in 120 minutes, followed by continuous infusion of 5-fluorouracil 2400 mg/m^2 in 46 hours, every 2 weeks) or mFOLFOXIRI plus bevacizumab (Bevacizumab 5 mg/kg in 15-30 minutes i.v., followed by oxaliplatin 85 mg/m^2 i.v. in 120 minutes, followed by irinotecan 165 mg/m^2 i.v. in 60 minutes, together with leucovorin 400 mg/m^2 i.v. in 120 minutes, followed by continuous infusion of 5-fluorouracil 2400 mg/m^2 in 46 hours, every 2 weeks).
Patients will be evaluated every 8 weeks by MRI or CT scan for disease status. The assigned systemic treatment should be continued for at least 6 months or earlier in case of resectability, progression of disease, unacceptable toxicity, or patient refusal. If after 6 months MDT concludes that the patient is still not resectable, it is highly unlikely that resectability will be achieved at all. Therefore the chemotherapy regimen may be reconsidered after 6 months of treatment.
In patients who will become resectable and undergo secondary surgery of liver metastases, the total duration of preoperative and postoperative treatment together should be 6 months. However, the postoperative chemotherapy regimen was determined by the investigator.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Liver Metastases
Keywords
Cetuximab, Bevacizumab, Triplet Chemotherapeutic Regimen, Colorectal Cancer, Liver Metastases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
386 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
mFOLFOXIRI plus Cetuximab
Arm Type
Experimental
Arm Title
mFOLFOXIRI plus Bevacizumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
mFOLFOXIRI plus Cetuximab
Intervention Description
cetuximab 500mg/m2 + oxaliplatin 85 mg/m2 + irinotecan 165 mg/m2 + folinic acid 400 mg/m2 + 5-fluorouracil 2400 mg/m2 46h infusion starting on day 1, every 2 weeks
Intervention Type
Drug
Intervention Name(s)
mFOLFOXIRI Plus Bevacizumab
Intervention Description
bevacizumab 5mg/kg + oxaliplatin 85 mg/m2 + irinotecan 165 mg/m2 + folinic acid 400 mg/m2 + 5-fluorouracil 2400 mg/m2 46h infusion starting on day 1, every 2 weeks
Primary Outcome Measure Information:
Title
Conversion resection rate of liver metastases
Description
Rate of conversion from initially unresectable liver metastases to resectable ones
Time Frame
up to 6 months
Secondary Outcome Measure Information:
Title
Objective Response Rate
Description
rate of objective response for therapy
Time Frame
up to 6 months
Title
Incidence of adverse events
Description
Incidence of adverse events
Time Frame
up to 6 months
Title
Progression-Free Survival
Description
Progression free survival
Time Frame
up to 3 years
Title
Overall Survival
Description
overall survival
Time Frame
up to 3 years
Title
Early tumor shrinkage
Description
The rates of tumor shrinkage by RECIST at 8 weeks
Time Frame
at 8 weeks
Title
Best deepness of response
Description
the maximum tumor shrinkage rates by RECIST during the treatment of the study
Time Frame
up to 6 months
Title
time interval from chemotherapy to hepatectomy
Description
Time interval from the beginning of treatment to hepatectomy
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
No
Eligibility Criteria
Inclusion Criteria:
The primary tumor was confirmed by histology as colorectal adenocarcinoma
Initially unresectable liver metastases suggested by MDT
RAS/BRAF gene wild-type states
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Life expectancy ≥ 3 months
Good hematological function: neutrophil ≥ 1.5x109 / L and platelet count ≥ 100x109 / L; HB ≥ 9g / dl (within one week before randomization)
Normal liver and kidney function: serum bilirubin ≤ 1.5x normal upper limit (ULN), alkaline phosphatase ≤ 5x ULN, serum transaminase (AST or ALT) ≤ 5x ULN (within one week before randomization);
Sign the written informed consent to participate in the experiment
Exclusion Criteria:
Patients with liver metastases from colorectal cancer who have previously received targeted therapy, chemotherapy, radiotherapy or interventional therapy
Known or suspected extrahepatic metastasis
Patients with known hypersensitivity to any component of the study treatment
Clinical related coronary heart disease or history of myocardial infarction in the last 12 months or left ventricular ejection fraction below normal range
Acute or subacute intestinal obstruction
Pregnancy (no pregnancy confirmed by serum / urine β - hCG) or breastfeeding.
Other malignant tumors within 5 years, except for those with skin basal cell carcinoma or cervical cancer
Known drug / alcohol abuse
No legal capacity or limited legal capacity
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jianmin Xu, MD, Ph.D.
Phone
86-21-64041990
Ext
692011
Email
xujmin@aliyun.com
First Name & Middle Initial & Last Name or Official Title & Degree
Wentao Tang, MD, Ph.D.
Phone
86-21-64041990
Email
tangwt1988@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jianmin Xu, MD, Ph.D.
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Zhongshan Hospital, Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianmin Xu, MD,Ph.D
First Name & Middle Initial & Last Name & Degree
Zhen Lou, M.D. Ph.D
First Name & Middle Initial & Last Name & Degree
Zhigang Wang, M.D. Ph.D
First Name & Middle Initial & Last Name & Degree
Tao Zhang, M.D. Ph.D
First Name & Middle Initial & Last Name & Degree
Sheng Wang, M.D. Ph.D
First Name & Middle Initial & Last Name & Degree
Kejing Huang, M.D. Ph.D
First Name & Middle Initial & Last Name & Degree
Minhao Yu, M.D. Ph.D
First Name & Middle Initial & Last Name & Degree
Zihua Chen, M.D. Ph.D
First Name & Middle Initial & Last Name & Degree
Yong Chen, M.D.
First Name & Middle Initial & Last Name & Degree
Rui Zhang, M.D.
First Name & Middle Initial & Last Name & Degree
Yifei Pan, M.D.
First Name & Middle Initial & Last Name & Degree
Chunkang Yang, M.D.
First Name & Middle Initial & Last Name & Degree
Yijiu Shi, M.D.
First Name & Middle Initial & Last Name & Degree
Guiying Wang, M.D.
First Name & Middle Initial & Last Name & Degree
Zhenning Wang, M.D.
First Name & Middle Initial & Last Name & Degree
Lingjun Zhu, M.D.
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Conversion Therapy of RAS/BRAF Wild-Type Colorectal Cancer Patients With Initially Unresectable Liver Metastases
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