| General information |
| Database: | DB00630 |
| Objective: | The aim of this clinical trial was to investigate safety and efficacy when combining cetuximab with bevacizumab and irinotecan in patients with recurrent primary glioblastoma multiforme (GBM). |
| Authors: | Hasselbalch B, et al |
| Title: | Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide: a phase II trial. |
| Journal: | Neuro Oncol. |
| Year: | 2010 |
| PMID: | 20406901 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | Cetuximab, bevacizumab
|
| Target: | NA
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | glioblastoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 13 |
| Therapeutic Combination Content: | Cetuximab+bevacizumab+irinotecan |
| Study Type: | Phase III Trial |
| Key Patients Feature: | Adult patients (age 18 years) with histologicallyproven primary GBM (WHO classification)38 andMRIverified recurrent or progressive disease (PD)were eligible for inclusion. Moreover, patients had to have progression within 6 months of finishing standardtreatment with concomitant radiotherapy and temozolomide followed by adjuvant temozolomide.1Reintroduction of temozolomide was not allowed.Debulking surgery was performed, if possible, beforeentering the study but no other tumor reductive treatments were accepted. Basic clinical and laboratoryevaluations were performed within 2 weeks and MRIscan within 4 weeks of starting study treatment.Eligibility criteria were: WHO performance status 0-2; 4 weeks from prior surgery and/or chemotherapy;life expectancy .3 months; neutrophils 1500/mm3;platelets 125 000/mm3; hemoglobin 6.2 mmol/L;ASAT and/or ALT , 3 upper limit of normal (ULN);bilirubin 1.5 ULN; cholesterol 7 mmol/L;normal creatinine clearance; and activated partialthromboplastin time (APTT) 35 seconds and/or international normalized ratio (INR) from 0.8 to 1.2. Fertilewomen had to use contraception |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Bevacizumab and irinotecan were administered IV every 2 weeks. The first 10 patients received bevacizumab 5 mg/kg, but this was increased to 10 mg/kg after interim safety analysis. Irinotecan dose was based on whether patients were taking enzymeinducing antiepileptic drugs or not: 340 and 125 mg/m(2), respectively. Cetuximab 400 mg/m(2) as loading dose followed by 250 mg/m(2) weekly was administered IV. |
| Primary End Point: | 6month progression free survival (PFS) |
| Secondary End Point: | NA |
| Patients Number: | 43 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | response rate of all patients based onintentiontotreat (ITT) (CR t PR) was 26% (95% CI:14%-41%; Table 2). Eleven of the patients included(n 43) Among evaluablepatients (n 32), best response was recorded after 2-4 treatment cycles. Both patients with CR hadminor tumor load at the initiation of study treatment |
| Disease Control Rate: | 0.66 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The 6month progression free survival probability was 30% |
| Median OS A vs. C: | 29 weeks (95% CI: 23-37 weeks). |
| Adverse Event(agent arm): | One patient had lacunar infarction, 1 patient had multiple pulmonary embolisms, and 3 patients had grade 3 skin toxicity, for which 1 patient needed plastic surgery. One patient was excluded due to suspicion of interstitial lung disease. Three patients had deepvein thrombosis; all continued on study after adequate treatment. |
| Conclusions: | Cetuximab in combination with bevacizumab and irinotecan in recurrent GBM is well tolerated except for skin toxicity, with an encouraging response rate. Hotheyver, the efficacy data do not seem to be superior compared with results with bevacizumab and irinotecan alone. |