Inclusion Criteria:
1. Patients with newly diagnosed histologically proven intracranial supratentorial GBM
or gliosarcoma (GS) will be eligible for this protocol. Patients will not be
eligible if the original histology was a grade II or III glioma and a subsequent
histological diagnosis of a GBM is made.
2. All patients must sign an informed consent indicating that they are aware of the
investigational nature of this study.
3. Diagnosis will have been established by biopsy or resection 14-28 days prior to
registration. In order to permit healing, patients should not receive Day 1 of
treatment until at least 14 days after surgery.
4. Patients must not have had prior cranial RT. 5. Patients must have a plan to begin partial brain RT on the same day as the first
dasatinib dose and the first dose of TMZ. Radiotherapy can be performed at either MD
Anderson or outside facilities. Radiotherapy must be given by external beam to a
partial brain field in daily fractions of 180 to 200 cGy, to a planned total dose to
the tumor of approximately 6000 cGy. Stereotactic radiosurgery and brachytherapy
will not be allowed.
6. Patients must not have received prior cytotoxic drug therapy, non-cytotoxic drug
therapy, or experimental drug therapy for brain tumors.
7. Patients must be >/= 18 years old.
8. A contrast enhanced brain scan should be performed within 14 days prior to
registration and on a corticosteroid dose that has been stable or decreasing for at
least 5 days. If the corticosteroid dose is increased between the date of imaging
and registration, then a new baseline MRI/CT is required. The same type of scan,
i.e., MRI or CT, must be used throughout the period of protocol treatment for tumor
measurement. The use of MRI rather than CT is preferred.
9. Patients must have a Karnofsky performance status of >/= 60.
10. Patients must have adequate bone marrow function (WBC >/= 3,000/µl, ANC >/=
1,500/mm^3, platelet count of >/= 100,000/mm^3, and hemoglobin >/= 10 gm/dl),
adequate liver function (SGOT, SPGT and bilirubin /= Lower Limit of Normal (LLN) and adequate renal
function (creatinine /= 60 cc/min/1.73 m^2)
before starting therapy. These tests must be performed within 14 days prior to
registration. Eligibility level for hemoglobin may be reached by transfusion.
11. Patients must be willing to forego other cytotoxic and non-cytotoxic drug therapy
against the tumor while enrolled in the study.
12. Women of childbearing potential must have a negative beta-HCG pregnancy test
documented within 14 days prior to registration. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she should inform her
treating physician immediately.
Exclusion Criteria:
1. Patients must not have received prior Gliadel wafers.
2. Patients must not have received any investigational agents within 30 days prior to
commencing study treatment.
3. Patients must not have 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.
4. 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.
5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection or psychiatric illness/social situations that would limit compliance with
study requirements.
6. Patients with the following invasive procedures: a) Major surgical procedure, open
biopsy or significant traumatic injury < 14 days prior to Day 1 therapy b)
Anticipation of need for major surgical procedures during the course of the study c)
Core biopsy within 7 days prior to Day 1 therapy.
7. Patients must not be pregnant/breastfeeding and must agree to practice adequate
contraception. Breastfeeding should be discontinued if the mother is treated with
dasatinib.
8. Patients with clinically significant cardiovascular disease: a) History of ischemic
or hemorrhagic stroke within past 6 months b) Uncontrolled hypertension, defined as
blood pressure >140/90 mm Hg or systolic BP >180 mm Hg if diastolic blood pressure
<90 mm Hg, on at least 2 repeated determinations on separate days within past 3
months c) Myocardial infarction, CABG or unstable angina within past 6 months d) New
York Heart Association grade III or greater congestive heart failure, serious
cardiac arrhythmia requiring medication, unstable angina pectoris within past 6
months. 9. ( 8. continued) e) Clinically significant peripheral vascular disease within past 6
months f) Pulmonary embolism, DVT, or other thromboembolic event within past 6
months. g) Diagnosed congenital long QT syndrome h) Any history of clinically
significant ventricular arrhythmias (such as ventricular tachycardia, ventricular
fibrillation, or Torsades de pointes) i) Prolonged QTc interval on pre-entry
electrocardiogram (> 450 msec) j) Subjects with hypokalemia or hypomagnesemia if it
cannot be corrected prior to dasatinib administration. 10. Evidence of bleeding diathesis or coagulopathy or INR >1.5. History of significant
bleeding disorder unrelated to cancer, including: a) Diagnosed congenital bleeding
disorders (e.g., von Willebrand's disease) b) Diagnosed acquired bleeding disorder
within one year (e.g., acquired anti-factor VIII antibodies) c) Ongoing or recent
(/= 2 weeks prior to initiation of dasatinib. It should also be noted whether
patients were or were not previously receiving EIAEDs and the last date of
administration of EIAEDs.
16. ( 15. continued) b) Antacids: Use of H2 blockers and proton pump inhibitors is
prohibited because systemic antacids (H2 inhibitors, proton pump inhibitors)
decrease dasatinib absorption. Patients who require antacids should use short
acting, locally active agents (e.g., Maalox, Mylanta etc.). However, these agents
should not be taken within either 2 hours before or 2 hours after the dasatinib
dose. This is particularly important in patients with glioblastoma who are
frequently on dexamethasone and prophylactic H2 blockers or proton pump inhibitors.
17. (15. continued) c) Anticoagulants/Anti-platelets: Patients on therapeutic
(treatment) dose of anticoagulants (e.g. warfarin, low molecular-weight heparin) are
not eligible. Patients are not allowed to take aspirin, clopidogrel, ticlopidine,
Aggrenox. Patients on prophylactic anticoagulation may be enrolled and treated on
study as long as their platelet count is monitored closely and maintained at >75,000
while they are receiving Dasatinib.
18. (15. continued) d) Ibuprofen and other NSAIDS: Ibuprofen and other non-steroidal
anti-inflammatory drugs (NSAIDS) can inhibit platelet function. Patients may not
take ibuprofen or other NSAIDs at study entry and must have stopped these agents
>/=7 days prior to starting dasatinib to allow for an appropriate wash-out period.
19. (15. continued) e) Inducers and Inhibitors of CYP3A4: Patients required to be on any
of those drugs will be excluded (with the exception of Dexamethasone, but all
efforts should be made to reduce the dose of dexamethasone). Patients may
discontinue drug at least 7 days prior to starting dasatinib.
20. (15. continued) f) Category I drugs that are generally accepted to have a risk of
causing Torsades de Pointes including: (Patients must discontinue drug at least 7
days prior to starting dasatinib) (1). quinidine, procainamide, disopyramide (2).
amiodarone, sotalol, ibutilide, dofetilide (3). erythromycin, clarithromycin (4).
chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide (5). cisapride,
bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine,
levomethadyl, pentamidine, sparfloxacin, lidoflazine.
