| General information |
| Database: | DB00588 |
| Objective: | They sought to determine the maximum tolerated dose (MTD) and doselimiting toxicity (DLT) of vandetanib combined with sirolimus. |
| Authors: | Chheda MG, et al |
| Title: | Vandetanib plus sirolimus in adults with recurrent glioblastoma: results of a phase I and dose expansion cohort study. |
| Journal: | J Neurooncol |
| Year: | 2015 |
| PMID: | 25503302 |
| Trial Design |
| Clinical Trial Id: | NCT00821080 |
| Agent: | Vandetanib and sirolimus
|
| Target: | NA
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | glioblastoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | Vandetanib+sirolimus |
| Study Type: | a phase I and dose expansion cohort study |
| Key Patients Feature: | patients were eligible for the present study if they wereadults (age 18 or greater) with recurrent GBM on noCYP3A4inducing drugs, previously treated with standardtherapy including resection if feasible, radiation and temozolomide, no more than three prior chemotherapies, na ¡§veto prior antiVEGF, antiEGF therapy or mTOR inhibitorsand had a Karnofsky performance status (KPS) C60 % andminimental status examination (MMSE) score [15.Patients must have been at least 3 months from the completion of radiation or radiosurgery and must have beenmaintained on a stable or decreasing corticosteroid regimenfor at least 3 days prior to the start of treatment. Laboratoryprerequisites included: normal ANC and platelets, renal, liver, and cardiac function. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Vandetanib and sirolimus were orally administered on a continuous daily dosing schedule in escalating dose cohorts. |
| Primary End Point: | MTD |
| Secondary End Point: | efficacy |
| Patients Number: | 22 |
| Trial Results |
| DLT_MTD: | MTD was 200 mg vandetanib plus 2 mg sirolimus. The DLT was elevated AST/SGOT. |
| Objective Response Rate: | For 19 patients who received at least one dose at the MTD, including seven from the phase I group, two had a partial response [10.5 %; 95 % CI (1, 33 %)]. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | In the dose expansion cohort, median progression free survival was 1.9 months [95 % CI (0.1, 1.9 months)]. For all patients, median progression free survival was 2.1 months [95 % CI (0.9, 3.1 months)] |
| Median OS A vs. C: | In the dose expansion cohort, median overall survival was 7.2 months [95 % CI (3.2, 8.8 months)]. For patients studied at all dose levels, median overall survival was 7.7 months [95 % CI (4.7, 9.3 months)] |
| Adverse Event(agent arm): | The most common toxicities were lymphopenia, fatigue, rash, and hypophosphatemia. |
| Conclusions: | Vandetanib and sirolimus can be safely coadministered on a continuous, daily dosing schedule. |