Bosutinib in Adult Patients With Recurrent Glioblastoma

Inclusion Criteria:

* 18 years of age or older
* Histologically confirmed WHO (World Health Organization) grade IV astrocytoma (glioblastoma). Patients with recurrent disease whose original pathology confirmed glioblastoma will not need re-biopsy. Patients with prior low-grade glioma or anaplastic glioma are eligible if histological assessment demonstrates transformation to GBM.
* The first-line regimen must have included, at a minimum, temozolomide and radiation.
* First or second episode of progressive disease.
* No more than two prior treatment regimens for progressive disease. Concurrent temozolomide and radiation followed by monthly cycles of temozolomide is counted as one regimen.
* For all study arms, patients must have at least 15 unstained slides or 1 tissue block available from a prior biopsy or surgery.
* All patients must have progressive disease on contrast-enhanced brain CT or MRI as defined by MacDonald Criteria, or have documented recurrent glioblastoma on diagnostic biopsy. Arm A patients may continue treatment in the post-operative period even if there is no residual contrast-enhancing tumor after surgery.
* For Arm A, patients must be candidates for surgical partial or gross-total resection.
* Interval of at least 2 weeks between prior surgical resection and adequate wound healing.
* Interval of at least 12 weeks from prior radiotherapy unless there is either a) histopathologic confirmation of recurrent tumor; b) new enhancement on MRI outside of the XRT (external beam radiation therapy) treatment field.
* Patients must have sufficient time for recovery from prior therapy
* Karnofsky Performance Status of 60% or greater
* Laboratory levels as outlined in the protocol
* Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation and for 3 months thereafter.

Exclusion Criteria:

* Participants may not be receiving any other investigational agents
* Previously treated with an anti-VEGF (anti-vascular endothelial growth factor) agent
* For subjects in Arm A: if the diagnostic pathology of the biopsy specimen is not consistent with recurrent glioblastoma then the subject will be taken off study and be replaced with another subject that meets the inclusion criteria and is eligible for surgical resection
* Any surgery within 2 weeks of baseline disease assessments, or not fully recovered from any side effects of previous procedures
* Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drug, such as the inability to take oral medications in tablet form.
* Any psychiatric or cognitive disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this protocol
* Concomitant use of CYP3A4/5 inhibitors during the treatment phase of the study and within 72 hours prior to starting study drug administration
* Concomitant use of CYP3A4/5 inducers, which include enzyme inducing antiepileptic drugs during treatment phase of the study and within 2 weeks prior to starting treatment.
* Uncontrolled or significant cardiovascular disease
* Prior stereotactic radiotherapy, convection enhanced delivery or brachytherapy as gliosis/scarring from these modalities may limit delivery
* Pregnant or breast feeding women
* HIV-positive individuals on combination antiretroviral therapy
* Other severe acute or chronic medical condition or laboratory abnormality