| Exclusion Criteria: | 1) Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years. (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
2) Radiotherapy within 4 weeks or temozolomide within 14 days prior to registration or failure to recover from adverse events of either radiotherapy or temozolomide
3) Patients may not be receiving any other investigational agents
4) Severe, active comorbidity, defined as follows: 1) Any clinically significant cardiovascular disease including the following: (1) Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months (2) Transmural myocardial infarction or ventricular tachyarrhythmia within the last 6 months (3) Prolonged QTc>480 msec (Fridericia correction) (4) Ejection fraction less than institutional normal (5) Major conduction abnormality (unless a cardiac pacemaker is present)
5) (4. cont'd) 2) Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration 3) Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
6) (4. cont') 4) Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive and dasatinib may interact with HAART.
7) Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because animal studies with dasatinib have shown embryolethality and fetal skeletal alterations at non-toxic maternal doses. Because there is an unknown but potential risk for adverse events in nursing human infants secondary to treatment of the mother with dasatinib, breastfeeding should be discontinued if the mother is treated with dasatinib.
8) History of allergic reactions attributed to compounds of similar chemical or biologic composition to dasatinib
9) Patients who require concurrent treatment with any medications or substances that are potent inhibitors or inducers of CYP3A4 are ineligible. 1) Anticonvulsants: Patients must not be taking hepatic enzyme inducing antiepileptic drugs (EIAEDs). If patients were previously on EIAEDs that have been discontinued, patients must have been off EIAEDs for >/= 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.
10) ( 9. cont'd) 2) Antacids: This is particularly important for patients with gliomas because such patients are often routinely prescribed H2 blockers, proton pump inhibitors, or locally-active antacids in association with corticosteroids. Because systemic antacids (H2 inhibitors, proton pump inhibitors) decrease dasatinib absorption, patients who require antacids should use shortacting, 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.
11) Use of antithrombotic and/or antiplatelet agents (e.g., warfarin, heparin, low molecular weight heparin, aspirin, clopidogrel, ticlopidine, Aggrenox)
12) Use of ibuprofen and other NSAIDs
13) Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain dasatinib tablets are excluded
14) Prior treatment with stereotactic radiosurgery (including Gamma-Knife, Cyberknife, or other variants) or brachytherapy. |