| General information |
| Database: | DB00637 |
| Objective: | Brain metastases (BMs) are associated with a poor prognosis. Standard treatment comprises wholebrain radiation therapy (WBRT). As neoangiogenesis is crucial in BM growth, combining angiogenesis inhibitors such as bevacizumab with radiotherapy is of interest. they aimed to identify the optimal regimen of bevacizumab combined with WBRT for BM forphase II evaluation and provide preliminary efficacy data. |
| Authors: | L¨¦vy C, et al |
| Title: | REBECA: a phase I study of bevacizumab and wholebrain radiation therapy for the treatment of brain metastasis from solid tumours. |
| Journal: | Ann Oncol. |
| Year: | 2014 |
| PMID: | 25274615 |
| Trial Design |
| Clinical Trial Id: | NCT01332929 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | advanced cancer with brain metastasis |
| Cancer Subtype: | brain metastasis from breast and lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 4 |
| Therapeutic Combination Content: | bevacizumab and wholebrain radiation therapy |
| Study Type: | openlabelphase I doseescalation trial |
| Key Patients Feature: | Eligible patients had measurable BM from solid tumours and EasternCooperative Oncology Group performance status 0-2. Patients with BM eligible for neurosurgery or stereotactic radiotherapy or with meningeal carcinomatosis or contraindications to bevacizumab (including a prior cardiacand/or thromboembolic event, haemorrhagic BM or uncontrolled hypertension) were ineligible |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients with unresectable BM from solid tumours received three cycles of bevacizumab at escalating doses [5, 10 and 15 mg/kg every 2 weeks at dose levels (DL) 0, 1 and 2, respectively] and WBRT (30 Gy/15 fractions/3 weeks) administered from day 15. DL3 consisted of bevacizumab 15 mg/kg with WBRT from day 15 in 30 Gy/10 fractions/2 weeks. Safety was evaluated using NCICTCAE version 3. BM response (RECIST 1.1) was assessed by magnetic resonance imaging at 6 weeks and 3 months after WBRT |
| Primary End Point: | the RP2D |
| Secondary End Point: | assess treatmentrelated parameters of BM regression by morphologic and functional magnetic resonance imaging (MRI) 6 weeks after treatment end |
| Patients Number: | 19 |
| Trial Results |
| DLT_MTD: | There were no DLTs. Grade 12 infield and outfield toxicities occurred for five and nine patients across all DLs, respectively, including three and six patients (including one patient with both, so eight patients overall) of nine patients in DL3;one of three treated at DL0, one of three at DL1, two of three at DL2 and six of seven at DL3, including one complete response. |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | 7.1 months [95% confidence interval (CI) 5.3- not reached] |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 13.3 months [95% CI 7.7-not reached). |
| Adverse Event(agent arm): | Grade 1-2 infield and outfield toxicities occurred for five and nine patients across all DLs, respectively, including three and six patients (including one patient with both, so eight patients overall) of nine patients in DL3. |
| Conclusions: | Bevacizumab combined with WBRT appears to be a tolerable treatment of BM. DL3 warrants further efficacy evaluation based on the favourable safetyefficacy balance. |