Lapatinib Ditosylate, Temozolomide, and Radiation Therapy in Treating Patients with Newly Diagnosed Glioblastoma Multiforme

Inclusion Criteria

• Patients will have histologically proven intracranial glioblastoma multiforme (GBM) or gliosarcoma (GS); this includes treatment-naive patients with prior tissue diagnoses of lower grade gliomas that have been upgraded to GBM after repeat resection
• Patients must have available archived tissues of 20-30 unstained slides; if frozen tissues are available, at least 200 mg would be preferred, but not mandatory for study eligibility
• Use of effective means of contraception (men and women) in subjects of child-bearing potential
• Cranial magnetic resonance imaging (MRI) or contrast computed tomography (CT) must have been performed within 21 days of study entry; the use of MRI rather than CT is preferred; the same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement; if the surgical procedure was a resection, cranial MRI or contrast CT performed within 96 hours of resection is preferred but not required; if the surgical procedure was a biopsy only, a head CT within 96 hours of the biopsy is acceptable; patients without measurable or assessable disease are eligible
• Patients must begin partial brain radiotherapy and temozolomide chemotherapy no sooner than 2 weeks and no later than 6 weeks from the surgery in which pathology was confirmed; if a patient elects to have a second surgery to obtain further resection, they will remain eligible for treatment as long as no treatment has been initiated prior to this surgery; in this case, initiation of treatment must begin within 2 to 6 weeks from the last surgery; tissue collection is preferred but not mandatory; patients may have radiotherapy administered at outside facilities; radiotherapy must be given within 2 days of lapatinib initiation and by external beam to a partial brain field in daily fractions of 2.0 Gy, to a planned total dose to the tumor of 60.0 Gy; stereotactic radiosurgery and brachytherapy will not be allowed
• Patients must be willing to forego other drug therapy against the tumor while being treated with pulse dosing of lapatinib and temozolomide and radiation and subsequently pulse dosing lapatinib and temozolomide
• All patients must sign an informed consent approved by the Institutional Review Board indicating that they are aware of the investigational nature of this study; patients must sign an authorization for the release of their protected health information
• A life expectancy > 12 weeks
• Patients must have a Karnofsky performance status of >= 60
• White blood cells (WBC) >= 3,000/ul (performed within 14 days prior to treatment initiation)
• Absolute neutrophil count (ANC) >= 1,500/mm^3 (performed within 14 days prior to treatment initiation)
• Platelet count of >= 100,000/mm^3 (performed within 14 days prior to treatment initiation)
• Hemoglobin >= 10 gm/dl; eligibility level for hemoglobin may be reached by transfusion (performed within 14 days prior to treatment initiation)
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 2.5 times upper limit of normal (ULN) (performed within 14 days prior to treatment initiation)
• Bilirubin =< 1.5 times ULN (performed within 14 days prior to treatment initiation)
• Creatinine =< 1.5 mg/dL (performed within 14 days prior to treatment initiation)

Exclusion Criteria

• Patients who received previous radiotherapy to the brain
• Patients with multifocal disease or leptomeningeal disease who require whole brain radiotherapy (WBRT)
• Patients who received cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy directed against the brain tumor; patients who received Gliadel wafers will be excluded; patients may have received or be receiving corticosteroids, analgesics, and other drugs to treat symptoms or prevent complications
• Patients who may be receiving any enzyme-inducing antiepileptic drugs (EIAED) within 2 weeks prior to registration, or any other prohibited medications within the washout period prior to registration
• Patients with any significant medical illnesses that in the investigator’s opinion cannot be adequately controlled with appropriate therapy or would compromise the patient’s ability to tolerate this therapy
• Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible
• Women who are pregnant (determined by high titer of serum beta-human chorionic gonadotropin [HCG]) or breast-feeding; (women with reproductive potential must practice adequate contraception)
• Patients who have any disease that will obscure toxicity or dangerously alter drug metabolism
• Patients who have serious uncontrolled inter-current medical illness including, but not limited to, ongoing or active infection requiring intravenous (IV) antibiotics and psychiatric illness/social situations that would limit compliance with study requirements, or disorders associated with significant immunocompromised state (human immunodeficiency virus [HIV], systemic lupus erythematosus [SLE], etc.)
• Patients who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)