A Biomarker and Phase II Study of GW572016 in Recurrent Malignant Glioma
- One of the most critical challenges facing glioblastoma translational research is
developing ways to predict, based on a patient's biopsy, which targeted inhibitor is most
likely to provide benefit. The studies outlined in this proposal are designed to determine
which glioblastoma patients are most likely to benefit from GW572106, and may provide a
blueprint for analyzing promising new pathway inhibitors in the future. We anticipate that
these studies will serve as the basis for biological endpoint based trials in the future.
Thus, the overall goal is to evaluate the efficacy of GW572016 in the treatment of recurrent
malignant gliomas in patients who are candidates for re-resection.
- Determine the 6-month progression-free survival rate for patients with recurrent or
progressive glioblastoma treated with GW572016.
- Determine whether GW572016 inhibits the phosphorylation of its cellular targets EGFR
and HER2, and the downstream PI3K-AKT and RAS-ERK signaling pathways in glioblastoma
patients in vivo.
- Determine tumor concentrations of GW572016.
- Assess overall progression free survival and safety.
- Patients with histologically proven intracranial tumors to include only glioblastoma
multiforme (GBM) and Gliosarcoma (GS). Patients will be eligible if the original
histology was low-grade glioma and a subsequent histological diagnosis of a GBM is
- Patients must be candidates for surgical re-resection (total, or sub-total) in order to
be eligible for this study. Following surgery, a scan should be done no later than 96
- Patients may be on a non-enzyme-inducing anti-epileptic drugs (Non-EIAED's). They may
not be on EIAED's. If previously on an EIAED, patient must be off of it for two weeks
prior to initiation of pre-operative drug.
- A Pre-Treatment blood sample (10ml) will be obtained in all patients for genotyping
- Pre- Operative: GW572016 will be administered at a starting dose of 750 mg orally BID
daily on an outpatient basis for 7-10 days. (This range is to allow flexibility for
planning surgery). GW572016 will be continued up to and including the evening before
- At the time of surgery 10ml of blood will be collected in EDTA containing tubes for
- Treatment may be instituted postoperatively as soon as patients have recovered from
effects of surgery and demonstrated wound healing. Treatment with GW572016
post-operatively should start no later than 28 days after surgery. GW572016 will be
administered at a starting dose of 750 mg orally BID daily on an outpatient basis.
GW572016 will be administered continuously; however, for the purposes of protocol
evaluations, a cycle will be defined as 28 days.
Masking: Open Label, Primary Purpose: Treatment
Determine 6-month progression-free survival of patients undergoing surgery for recurrent progressive glioblastoma multiforme or gliosarcoma treated with lapatinib.
Elise C Kohn, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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