GW572016 to Treat Recurrent Malignant Brain Tumors
This study will examine whether an experimental drug called GW572016 can delay tumor growth in patients with glioblastoma multiforme (GMB, a malignant brain tumor). GW572016 is believed to affect cancer cell function by interfering with the internal signaling needed for the cancer to grow. The study will also determine whether the presence of specific proteins in the tumor can predict what effects GW572016 will have on the tumor.
Patients 18 years of age and older with GMB whose brain tumor does not respond to standard medical treatment and who can undergo surgery for their tumor may be eligible for this study. Candidates are screened with a physical examination and neurocognitive examination, blood tests, electrocardiogram (EKG), echocardiogram (ultrasound test of heart function) or MUGA scan (nuclear medicine test of heart function), magnetic resonance imaging (MRI) of the head, and computed tomography (CT) of the head. CT uses x-rays and MRI uses a magnetic field and radio waves to show brain structure.
Participants undergo the following tests and procedures:
- MRI and blood tests before surgery.
- Surgery to remove the brain tumor.
- Follow-up MRIs every 8 weeks after surgery.
- Follow-up echocardiograms or MUGA scans every 8 weeks after surgery.
- GW572016 treatment starting 7-10 days before surgery and continuing until the patient or doctor decides it is in the patient's best interest to stop it or until the tumor worsens. (The drug is stopped temporarily for surgery and a healing period after surgery.)
- Blood tests every 2 weeks to evaluate the effects of GW572016 on the body.
- Blood test before the first GW572016 treatment and at the time of surgery to assess the effect of the drug on the cells and to determine how much drug is present in the blood at the time of surgery.
Participants are followed in clinic at least monthly while taking GW572016. While on treatment they keep a diary documenting their daily treatments. The diary is collected at the monthly follow-up exams. After the treatment ends, patients are contacted periodically by the research staff for the rest of their lives to follow the long-term effects of the study.
|Glioma Brain Tumor Glioblastoma Multiforme GBM Gliosarcoma GS||Drug: lapatinib ditosylate Procedure: Adjuvant therapy Procedure: Conventional surgery Procedure: Neoadjuvant therapy||Phase 2|
|Study Design:||Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Biomarker and Phase II Study of GW572016 in Recurrent Malignant Glioma|
- Determine 6-month progression-free survival of patients undergoing surgery for recurrent progressive glioblastoma multiforme or gliosarcoma treated with lapatinib.
|Study Start Date:||March 30, 2005|
|Study Completion Date:||November 30, 2012|
|Primary Completion Date:||December 5, 2007 (Final data collection date for primary outcome measure)|
- 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 made.
- 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 hours
- 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 surgery.
- At the time of surgery 10ml of blood will be collected in EDTA containing tubes for pharmacodynamic analysis
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00107003
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Teri N Kreisl, M.D.||National Cancer Institute (NCI)|