| General information |
| Database: | DB00302 |
| Objective: | Although CRC is the third most commonly diagnosed cancer in the United States, secondline CRC treatment is limited. In this trial they examined the efficacy and safety of linifanib, an oral, potent, selective tyrosine kinase inhibitor of vascular endothelial growth factor and plateletderived growth factor receptor families, with mFOLFOX6, compared with bevacizumab and mFOLFOX6, in previously treated metastatic CRC. |
| Authors: | O'Neil BH, et al |
| Title: | Randomizedphase II openlabel study of mFOLFOX6 in combination with linifanib or bevacizumab for metastatic colorectal cancer. |
| Journal: | Clin Colorectal Cancer |
| Year: | 2014 |
| PMID: | 25066269 |
| Trial Design |
| Clinical Trial Id: | NCT00707889 |
| Agent: | linifanib
|
| Target: | Macrophage colonystimulating factor 1
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | mFOLFOX6+ linifanib/bevacizumab |
| Study Type: | a phase II, randomized, activecontrolled, openlabel, multicenter trial |
| Key Patients Feature: | more than and equal to 18 years of age with measurable histologically or cytologically confirmed recurrent or metastatic adenocarcinoma of the colon or rectum not amenable to surgical resection with a curative intent. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | bevacizumab (10 mg/kg, intravenous)(arm A), lowdose linifanib (7.5 mg)(arm B), or highdose linifanib (12.5 mg)(arm C) |
| Treatment Info: | patients with advanced CRC previously treated with fluoropyrimidine or irinotecan received bevacizumab (10 mg/kg, intravenous), lowdose linifanib (7.5 mg), or highdose linifanib (12.5 mg), with mFOLFOX6. |
| Primary End Point: | progression free survival (PFS). |
| Secondary End Point: | overall survival (OS), objective response rate (ORR), and safety. |
| Patients Number: | 148 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | ORRs were similar (bevacizumab, 34.7% [95% CI, 21.749.6]; lowdose linifanib, 24.0% [95% CI, 13.138.2]; highdose linifanib, 22.4% [95% CI, 11.836.6]). Median cycles of 5fluorouracil were reduced in the linifanib arms, versus the bevacizumab arm. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | No statistically significant differences in PFS occurred between bevacizumab and linifanib doses (low, hazard ratio [HR], 1.453 [95% confidence interval [CI], 0.8302.539]; high, HR, 1.257 [95% CI, 0.6722.351]). |
| Median OS A vs. C: | Median OS values were similar for bevacizumab and highdose linifanib (bevacizumab, 16.5 months [95% CI, 13.0not available]; highdose linifanib, 16.4 months [95% CI, 11.921.7]; lowdose linifanib, 12.0 months [95% CI, 10.113.0]). |
| Adverse Event(agent arm): | Grade 3/4 adverse event occurrences were more frequent with linifanib. Palmarplantar erythrodysesthesia, hypothyroidism, and thrombocytopenia were more common with highdose linifanib than bevacizumab. |
| Conclusions: | Combining linifanib with mFOLFOX6 as a secondline treatment for metastatic CRC did not improve PFS, radiographic findings, or duration of response versus bevacizumab and mFOLFOX6. |