Lapatinib Ditosylate Before Surgery in Treating Patients With Recurrent High-Grade Glioma

Recurrent Glioblastoma Clinical Trial

Official title: Drug Distribution and Pharmacodynamic Study of Pulsatile Lapatinib in Surgically Accessible EGFR-Amplified Recurrent High-Grade Glioma

Status Active, not recruiting

Clinical Trial Summary

This pilot phase I clinical trial studies how well lapatinib ditosylate before surgery works in treating patients with high-grade glioma that has come back after a period of time during which the tumor could not be detected. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To achieve an intratumoral lapatinib (lapatinib ditosylate) concentration of at least 1.5 uM in at least 70% of patients 3 hours after the last dose of pulsatile lapatinib. (Group A) II. To determine the pharmacodynamic (PD) effect of pulsatile lapatinib (at pulsatile maximum tolerated dose [MTD]) on epidermal growth factor receptor (EGFR) phosphorylation (using Mesoscale Discovery enzyme-linked immunosorbent assay [ELISA] assay for total and phospho-EGFR). (Group A and Reference Group)

SECONDARY/EXPLORATORY OBJECTIVES:

Ia. To evaluate the safety profile of pulsatile lapatinib in pre-operative patients with EGFR amplified recurrent high-grade glioma. (Group A and Reference Group) Ib. To evaluate acute and late toxicities associated with pulsatile lapatinib. (Group A and Reference Group) II. To determine the effect of lapatinib on tumor cell proliferation (marker of proliferation Ki-67 [KI-67] staining). (Group A compared to Reference Group) III. To determine the ex-vivo sensitivity of tumor sphere cultures to lapatinib. (Group A and Reference Group) IV. To assess tumor objective response rate (ORR). (Group A and Reference Group) V. To estimate overall survival (OS). (Group A and Reference Group) VI. To estimate progression-free survival. (Group A and Reference Group)

OUTLINE: Patients are assigned to 1 of 2 treatment groups.

GROUP A: Patients receive lapatinib ditosylate orally (PO) twice daily (BID) on days -2 to 0. Within 3-5 hours after last dose of lapatinib ditosylate, patients undergo surgical resection of tumor on day 0. Within 30 days of surgical resection of tumor, patients receive lapatinib ditosylate BID for 2 days every 7 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

REFERENCE GROUP: Patients undergo surgical resection of tumor on day 0. Within 30 days of surgical resection of tumor, patients receive lapatinib ditosylate BID for 2 days every 7 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for at 30 days, every 2 months for 2 years, and every 6 months thereafter. ;

Related Conditions & MeSH terms

• Anaplastic Astrocytoma
• Anaplastic Ependymoma
• Anaplastic Oligodendroglioma
• Astrocytoma
• Brain Neoplasms
• Ependymoma
• Glioblastoma
• Glioma
• Gliosarcoma
• Mixed Glioma
• Oligodendroglioma
• Recurrence
• Recurrent Adult Brain Neoplasm
• Recurrent Glioblastoma

• NCT number: NCT02101905
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 13, 2014
• Completion date: October 19, 2024