| General information |
| Database: | DB00602 |
| Objective: | They evaluated BEV and IRI as neoadjuvant and adjuvant treatment combined with TMZbased chemoradiation for unresectable GB. |
| Authors: | Chauffert B, et al |
| Title: | Randomizedphase II trial of irinotecan and bevacizumab as neoadjuvant and adjuvant to temozolomidebased chemoradiation compared with temozolomidechemoradiation for unresectable glioblastoma: final results of the TEMAVIR study from ANOCEF . |
| Journal: | Ann Oncol. |
| Year: | 2014 |
| PMID: | 24723487 |
| Trial Design |
| Clinical Trial Id: | NCT01022918 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | glioblastoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | irinotecan and bevacizumab as neoadjuvant and adjuvant to temozolomidebased chemoradiation |
| Study Type: | a randomized I:I noncomparativephase II trial |
| Key Patients Feature: | Eligible patients had de novo supratentorial GB that was histologicallyconfirmed after strereotaxic or surgical biopsy. Patient ages ranged from 18and 70 years. Karnofsky index (KI) performance status had to be 50, orhigher. Tumour was judged nonresectable. Neurological status was scoredaccording to the MRC criteria with no (0), mild (1, 2), or severe (3, 4) impairment of neurological functions [5]. RPA class was scored according toEORTC [3]. Only class V patients were enrolled. Urine protein test had to benegative, or urine protein concentration <1 g/24 h. Systolic arterial bloodpressure was less than and equal to 170 mmHg, under treatment if required. Enrolment was notallowed for patients with cardiovascular contraindications to BEV, ongoinganticoagulant or antiaggregant treatment, previous digestive haemorrhage, and/or gastroduodenal ulcer |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | The experimental arm (BEV/IRI) consisted of neoadjuvant intravenous BEV, 10 mg/kg, and IRI, 125 mg/m(2), every 2 weeks for four cycles before radiotherapy (RT) (60 Gy), concomitant oral TMZ, 75 mg/m(2)/day, and BEV, 10 mg/kg every 2 weeks. Adjuvant BEV and IRI were given every 2 weeks for 6 months. The control arm consisted of concomitant oral TMZ, 75 mg/m(2)/day during RT, and 150200 mg/m(2) for 5 days every 28 days for 6 months. The use of BEV was allowed at progression in the control arm. |
| Primary End Point: | an expected 6month PFS of 66% (H1) in the experimental BEV/IRI arm |
| Secondary End Point: | overall survival (OS), and safety |
| Patients Number: | 120 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | PFS6 was 7.1 months in BEV/IRI versus 5.2 months in the control arm. |
| Median OS A vs. C: | The median overall survival was not different between the two arms (11.1 months). |
| Adverse Event(agent arm): | Main toxicities were three fatal intracranial bleedings, three bile duct or digestive perforations/infections (1 fatal), and six thrombotic episodes in the BEV/IRI arm, whereas there was one intracranial bleeding, two bile duct or digestive perforations/infections (1 fatal), and one thrombotic episode in the control arm. |
| Conclusions: | Neoadjuvant and adjuvant BEVIRI, combined with TMZradiation, is not recommended for further evaluation in the firstline treatment of unresectable GB. |