Phase 2
N=57
Phase (Ph) II Bevacizumab + Erlotinib for Patients (Pts) With Recurrent Malignant Glioma (MG)
Glioblastoma · Gliosarcoma
Bottom Line
View on ClinicalTrials.gov: NCT00671970 ↗Enrolled (actual)
57
Serious AEs
35.1%
Results posted
May 2013
Primary outcome: Primary: 6 Month Progression-free Survival — .438; .292 proportion of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Bevacizumab and Erlotinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Duke University
- Primary completion
- Nov 2008
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 6 Month Progression-free Survival |
.438; .292 | — |
| SECONDARY Radiographic Response |
1; 1; 9; 11 | — |
| SECONDARY Pharmacokinetics of Erlotinib: Cmax |
794; 1323; 1320; 1400 | — |
| SECONDARY Pharmacokinetics of Erlotinib: AUC |
11072; 15611; 26072; 21421 | — |
| SECONDARY Association of Biomarkers and One-year Survival - Epidermal Growth Factor (EGFR) |
7; 0 | 1.0 |
| SECONDARY Association of Biomarkers and One-year Survival - EGFR vIII |
1; 7 | .613 |
| SECONDARY Association of Biomarkers and One-year Survival - Phosphatase and Tensin Homologue (PTEN) |
1; 7 | 1.0 |
| SECONDARY Association of Biomarkers and One-year Survival - Phosphorylated Protein Kinase B (pAKT) |
6; 1 | 1.0 |
| SECONDARY Association of Biomarkers and One-year Survival - Phosphorylated Mitogen-activated Protein Kinase (pMAPK) |
5; 1 | 1.0 |
| SECONDARY Association of Biomarkers and One-year Survival - Vascular Endothelial Growth Factor (VEGF) |
40; 60 | .179 |
| SECONDARY Association of Biomarkers and One-year Survival - VEGFR-2 |
50; 120 | .008 sig |
Summary
Primary objective:
To estimate 6-month progression free survival probability of pts w recurrent malignant gliomas treated w erlotinib + bevacizumab.
Secondary Objectives:
To evaluate safety & tolerability of erlotinib + bevacizumab among pts w recurrent malignant gliomas To evaluate radiographic response of pts w recurrent malignant gliomas treated w erlotinib + bevacizumab To evaluate pharmacokinetics of erlotinib when administered to pts w recurrent malignant gliomas; & to examine relationship of clinical response to Epidermal Growth Factor (EGFR) expression, amplification, & v-III mutation, phosphatase and tensin homolog (PTEN) expression, vascular endothelial growth factor (VEGF) expression, vascular endothelial growth factor receptor 2 (VEGFR-2) & phosphorylated protein kinase B (PKB/Akt) in archival tumor samples
Eligibility Criteria
Inclusion Criteria
- Pts have histologically confirmed diagnosis of recurrent/progressive WHO gr III & IV MG & meet following inclusion criteria:
- Age >18 yrs
- Interval of >4 wks since prior surgery
- Interval of >4 wks since prior external beam radiation therapy (XRT) or chemo, unless there is unequivocal evidence of progressive disease & pts have recovered from all anticipated toxicity of most recent therapy
- Karnofsky performance status score >60
- Hematocrit > 29 percent, absolute neutrophil count (ANC) >1,500 cells/microliter, platelets >100,000 cells/microliter
- Serum creatinine 6 wks must have elapsed since their last dose
- Signed informed consent approved by Institutional Review Board (IRB) prior to patient entry;
- If sexually active, pts must agree to take contraceptive measures for duration of treatments
Exclusion Criteria
- Prior therapy w either bevacizumab/EGFR-directed agents
- >3 prior recurrences
- Pregnancy/breast feeding
- Co-medication w immuno-suppressive agents other than corticosteroids including but not limited to cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil
- Evidence of central nervous system (CNS) hemorrhage on baseline MRI on CT scan
- Pts who require therapeutic anti-coagulation
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics & psychiatric illness/social situations that would limit compliance w study requirements, or disorders associated w significant immunocompromised state
- Pts w another primary malignancy that has required treatment within past year
- Pts w acute/chronic renal insufficiency/those w acute renal insufficiency of any severity due to hepato-renal syndrome/in peri-operative liver transplantation period
Data sourced from ClinicalTrials.gov (NCT00671970). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.