| General information |
| Database: | DB00632 |
| Objective: | they evaluated the antitumor activity and safety of erlotinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor, plus sirolimus, an inhibitor of the mammalian target of rapamycin, among patients with recurrent glioblastoma (GBM) in a phase 2, openlabel, singlearm trial. |
| Authors: | Reardon DA, et al |
| Title: | Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma. |
| Journal: | J Neurooncol. |
| Year: | 2010 |
| PMID: | 19562254 |
| Trial Design |
| Clinical Trial Id: | NCT0062243 |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | glioblastoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | Addition of bevacizumab to standard radiation therapy and daily temozolomide |
| Study Type: | Phase II trial |
| Key Patients Feature: | patients were required to have histologically confirmedGBM that was radiographically progressive following priorradiation or chemotherapy. Additional enrollment criteriaincluded: age at least 18 years; KPS C 70%; stable corticosteroid dose for at least 1 week prior to therapy initiation; hematocrit [29%; absolute neutrophil count[1, 500 cells/ll; platelet count [100, 000 cells/ll; andserum creatinine, aspartate aminotransferase and bilirubin1.5 times the institutional upper limit of normal. Patientswere also required to be at least 2 weeks from prior surgical resection, 12 weeks from prior radiotherapy (unlesshistopathologic confirmation of recurrent GBM wasobtained or new enhancement outside the radiation fieldwas demonstrated on MRI) and 4 weeks from prior chemotherapy (6 weeks for nitrosoureas). Patients treated withprior antiangiogenic therapy were eligible, however aminimum of 6 weeks was required from prior bevacizumabdosing. |
| Biomarker: | Archival tumor samples were assessed for EGFR, EGFRvIII, PTEN, pAKT and pS6. |
| Biomark Analysis: | Tumor markers failed to show an association with PFS except for increased pAKT expression which achieved borderline significance (P = 0.045). |
| Control Group Info: | single arm |
| Treatment Info: | Thirtytwo patients received daily erlotinib and sirolimus. The doses of erlotinib and sirolimus were 150 mg and 5 mg for patients not on concurrent CYP3Ainducing antiepileptics (EIAEDS), and 450 mg and 10 mg for patients on EIAEDS. Evaluations were performed every two months. |
| Primary End Point: | 6month progression free survival |
| Secondary End Point: | safety and overall survival |
| Patients Number: | 32 |
| Trial Results |
| DLT_MTD: | The most common grade C2 adverseevents were rash (59%), mucositis (34%) and diarrhea(31%). Grade 3 or higher events were rare |
| Objective Response Rate: | Best radiographicresponse included stable disease in 15 patients(47%); no patients achieved either a CR or PR. The estimated6month progression free survival was 3.1% for allpatients. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 8.4 weeks (95% CI, 3.9-12.1 weeks). Median PFS for patients who received prior bevacizumab (n = 7) was 4.0 weeks (95% CI: 3.6, 7.0), while the median PFS for those who did not receive prior bevacizumab (n = 25) was 7.4 weeks (95% CI: 3.9, 11.9) (P = 0.18). |
| Median OS A vs. C: | 33.8 weeks (95% CI, 21.953.6 weeks) |
| Adverse Event(agent arm): | The most common grade C2 adverse events were rash (59%), mucositis (34%) and diarrhea (31%). Grade 3 or higher events were rare. |
| Conclusions: | Erlotinib plus sirolimus was well tolerated but had negligible activity among unselected recurrent GBM patients. |