Safety Study of Pritumumab in Brain Cancer
brief summary
Pritumumab is a human IgG1 kappa antibody that binds to a malignant tumor associated antigen, ecto domain-vimentin (EDV) which is expressed in a variety of tumor cells. Pritumumab was shown to have relatively high reactivity with brain cancer cell lines, while no reactivity was demonstrated with normal neurons, astrocytes or fetal cerebral cells. Pritumumab has notable antibody-dependent cellular cytotoxicity (ADCC), brain tumor penetration and antitumor activity in nude mouse human xenograft models. Primary Objectives \- To determine the safety and/or tolerability and the recommended Phase 2 dose (RP2D) of escalating, intravenously (IV) administered Pritumumab doses in patients with recurrent gliomas or with brain metastases. Secondary Objectives * To determine pharmacokinetics and pharmacodynamics of Pritumumab * To identify preliminary signals of anti-tumor response to Pritumumab * To explore disease-related, patient-reported outcomes
detailed description
This is an open-label, Phase 1, outpatient, dose escalation study of Pritumumab in patients with brain cancer who have failed prior therapy and have no other available options. In the first part of the study, escalating doses of Pritumumab of 1.6, 4.8, 8.0, 12.0, and 16.2 mg/kg will be administered in a sequential, safety-driven manner to eligible patients according to standard 3+3 scheme, as an 1-hour IV infusion on Days 1, 8, 15, and 22 of each 28-day treatment cycle. The dose levels may be modified upon obtained results. Once the maximum tolerated dose (MTD) is determined, an expansion cohort including 6-12 patients in selected tumor type at a dose equal or below to MTD is planned to determine the recommended Phase 2 dose (RP2D). A total of 42 patients may be administered with Pritumumab in this study.
Patients will be treated with Pritumumab for a maximum of 6 cycles or until cancer progression or unacceptable toxicity. Patients will be followed after treatment completion every four months or until death or lost to follow-up. Standard clinical, laboratory and functional assessments will be employed to monitor for safety, tolerability and tumor response, including blood sampling for clinical biochemistries, pharmacokinetics, CSF and tissue samples, at frequency specified by the protocol. Patient-reported outcomes will also be assessed.
official title
A Phase 1, Sequential Cohort, Open-Label, Dose-Escalation Study of the Safety and CNS Exposure of Pritumumab in Patients with Brain Cancer