FOLFOXIRI With or Without Bevacizumab as First-line Treatment for Unresectable Liver-only Metasta… (NCT02350530) | Clinical Trial Compass
UnknownPhase 2
FOLFOXIRI With or Without Bevacizumab as First-line Treatment for Unresectable Liver-only Metastatic Colorectal Cancer Patients With RAS Mutation-type
China138 participantsStarted 2015-01
Plain-language summary
BACKGROUND:
For patients with liver-limited metastatic colorectal cancer (mCRC), complete resection of liver metastases is the only potentially curative treatment. The current goal of medical treatment for colorectal cancer with initially unresectable liver metastases is to maximize the rate of secondary resection and prolong overall survival (OS). A strong correlation was found between response rate and secondary resection rate of metastases, and the triple drugs combination of infusional 5-fluorouracil/leucovorin (5-FU/LV), irinotecan, and oxaliplatin (FOLFOXIRI) was recommended can be used in selected patients with potentially resectable metastases in order to improve response rate and make resection more possible. The addition of a anti-VEGFs monoclonal antibody such as bevacizumab to chemotherapy has been shown to increase response rate, resection rate and improve OS in the first-line treatment of mCRC patients. The efficacy and safety of bevacizumab in addition to triplet drugs were previously tested in OLIVIA trial, the resection rate of liver metastases of 49% was reported, and the response rate was 81%; most common grade 3-4 adverse events was neutropenia. On the basis of such promising results, we conducted the present randomized study to explore whether FOLFOXIRI plus bevacizumab compared with FOLFOXIRI alone as first-line treatment could improve radical resectability in patients with RAS mutation-type, unresectable liver-only metastatic colorectal cancer.
OBJECTIVE:
The primary objective of the FOBULM study is to evaluate the efficacy of FOLFOXIRI plus bevacizumab compared to FOLFOXIRI alone in patients with initially unresectable liver-limited RAS mutation-type mCRC.
Secondary objectives are safety and tolerability of the treatment, efficacy in terms of objective response rate (ORR), OS, progression free survival (PFS), quality of life and an assessment of biomarkers for predictive response and prognosis.
Who can participate
Age range18 Years – 70 Years
SexALL
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Inclusion criteria
✓. Willing and able to provide written informed consent
✓. Histological or cytological documentation of adenocarcinoma of the colon or rectum.
✓. Male or female subjects \> 18 years \< 70 of age.
✓. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
✓. There must be documentation by CT scan, MRI, or intraoperative palpation that the patient has evidence of metastases confined to the liver.
✓. The liver metastases must have been assessed by multidisciplinary team including hepatic surgeon approved to participate in the study to be unresectable based on at least one of the four criteria: 1. All of the liver metastases can not be completed resected with negative margins; 2. No ability to preservation of two contiguous hepatic segments; 3. No ability to preservation of adequate vascular inflow and outflow as well as biliary drainage; 4. Complete resection would require greater than 70% of the liver parenchyma to be removed.
✓. The colorectal primary tumor or metastatic tumor must be determined to be KRAS (exon 2 at codon 12 and 13; exon 3 at codon 59 and 61; exon 4 at codon 117 and 146) or NRAS (exon 2 at codon 12 and 13; exon 3 at codon 59 and 61; exon 4 at codon 117 and 146) mutation-type.
. Primary tumor and regional nodes were resected with clear surgical margins or; unresected primary tumor with plan to radical resect the primary tumor.
Exclusion criteria
✕. Any evidence of extrahepatic metastases, lymph node (including portal lymph nodes) metastases and primary tumor recurrence.
✕. Previous hepatic resection and/or ablation, hepatic arterial infusion therapy, radiation therapy to the liver.
✕. Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization.
✕. Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
✕. Unresolved toxicity higher than CTCAE v.4.0 Grade 1 attributed to any prior therapy/procedure.
✕. Subjects with known allergy to the study drugs or to any of its excipients.
✕. Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.