| General information |
| Database: | DB00891 |
| Objective: | Thisphase 1 clinical trial was conducted to determine the safety, maximumtolerated dose (MTD), and pharmacokinetics of imatinib, bevacizumab, and metronomic cyclophosphamide in patients with advanced colorectal cancer (CRC). |
| Authors: | Kelley RK, et al |
| Title: | a phase 1 trial of imatinib, bevacizumab, and metronomic cyclophosphamide in advanced colorectal cancer. |
| Journal: | Br J Cancer. |
| Year: | 2013 |
| PMID: | 24022191 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | imatinib, bevacizumab, and metronomic cyclophosphamide
|
| Target: | NA
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | imatinib, bevacizumab |
| Study Type: | a phase I with pharmacokinetic study |
| Key Patients Feature: | histologically confirmed diagnosis of solid tumor refractory to standard therapy or for whom no standard therapy existed; age more than and equal to 18 years; life expectancy more than and equal to 3 months |
| Biomarker: | Circulating tumour, endothelial, or immune cells |
| Biomark Analysis: | Circulating tumour, endothelial, or immune cells were not associated with progression free survival. |
| Control Group Info: | single arm |
| Treatment Info: | CCI779 given as a weekly 30 minutes intravenous (I.V.) infusion. |
| Primary End Point: | safety, tolerability, and pharmacokinetic parameters |
| Secondary End Point: | NA |
| Patients Number: | 35 |
| Trial Results |
| DLT_MTD: | Maximumtolerated doses were cyclophosphamide 50 mg q.d., imatinib 400 mg q.d., and bevacizumab 5 mg kg(1) i.v. every 2 weeks. Doselimiting toxicities (DLTs) included nausea/vomiting, neutropaenia, hyponatraemia, fistula, and haematuria. The DLT window required expansion to 42 days (1.5 cycles) to capture delayed toxicities |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 1.88 months (95% confidence interval: 1.85, 3.60) |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Doselimiting toxicities (DLTs) included nausea/vomiting, neutropaenia, hyponatraemia, fistula, and haematuria. The DLT window required expansion to 42 days (1.5 cycles) to capture delayed toxicities. |
| Conclusions: | The combination of metronomic cyclophosphamide, imatinib, and bevacizumab is safe and tolerable without significant drug interactions. A subset of patients experienced prolonged stable disease independent of dose level |