Inclusion Criteria:

- Patients will be included in the study based on the following criteria:

- Patients will have histologically proven intracranial Glioblastoma Multiforme (GBM)
or gliosarcoma (GS). This includes treatment-naïve 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 200mg 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 MRI or contrast 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 5 weeks from the surgery in which tissue was
collected. Patients with GBM diagnosis from surgeries in which tissue was not
collected will be eligible after repeat surgery performed to collect tissue, as long
as no treatment has been initiated prior to surgery in which tissue was collected.
In this case, initiation of treatment must begin within 2 to 5 weeks from the last
surgery. Patients may have radiotherapy administered at outside facilities
according to the specified guidelines (Appendix F). 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 in
accordance with Appendix F. 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.

- Patients must be > 18 years old, and with a life expectancy > 12 weeks.

- Patients must have a Karnofsky performance status of > 60.

- Patients must have adequate bone marrow function (WBC > 3,000/µl, ANC > 1,500/mm3,
platelet count of > 100,000/mm3, and hemoglobin > 10 gm/dl) and the test must be
performed within 14 days prior to treatment initiation. Eligibility level for
hemoglobin may be reached by transfusion.

- Patients must have adequate liver function (AST, ALT < 2.5 times ULN, and bilirubin <
1.5 times ULN) and the test must be performed within 14 days prior to treatment
initiation.

- Patients must have adequate renal function (creatinine < 1.5 mg/dL) before starting
therapy and the test must be performed within 14 days prior to treatment initiation.

EXCLUSION CRITERIA

- Patients who received previous radiotherapy to the brain.

- 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 EIAED (see Appendix C) within 2 weeks prior to
registration, or any other prohibited medications within the Washout Period per
Appendix D prior to registration. See section 6.5 for seizure medication
managements.

- 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-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 IV antibiotics and psychiatric
illness/social situations that would limit compliance with study requirements, or
disorders associated with significant immunocompromised state (HIV, 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).