Bosutinib in Adult Patients With Recurrent Glioblastoma
Condition: Glioblastoma
MeSH terms: Glioblastoma
Intervention: bosutinib
Intervention description: Taken orally
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: bosutinib; SKI-606

Summary:

      For many brain tumors, one reason that chemotherapy drugs might not be effective is that the
      drug may not be able to get into the brain tumor and kill the cancer cells. The brain is
      protected by a layer called the blood brain barrier. This barrier prevents substances from
      entering. The purpose of this research study is to determine if bosutinib can get past the
      blood brain barrier and into the brain tumor, and to see how well bosutinib works in killing
      cancer cells.
    

Eligibility criteria:

        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