Gossypol in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme
Condition: Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor
MeSH terms: Glioblastoma; Gliosarcoma; Recurrence
Intervention: R-(-)-gossypol acetic acid; laboratory biomarker analysis
Intervention description: Given PO; Correlative studies
Intervention MeSH terms: Acetic Acid; Retinol acetate; Gossypol acetic acid; Gossypol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well gossypol works in treating patients with progressive
      or recurrent glioblastoma multiforme. Gossypol may stop the growth of tumor cells by blocking
      some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed supratentorial glioblastoma multiforme
             which is progressive or recurrent after radiation therapy ± chemotherapy; patients
             with previously low grade glioma who progressed after radiotherapy ± chemotherapy and
             are biopsied and found to have glioblastoma multiforme are eligible

          -  Patients must have tumor tissue form completed and signed by a pathologist

          -  Patients must have measurable contrast enhancing progressive or recurrent glioblastoma
             multiforme by MRI or CT imaging (Within 14 days before starting treatment)

          -  Patients must have recovered from toxicity of prior therapy; an interval of at least 3
             months must have elapsed since the completion of the most recent course of radiation
             therapy, while at least 3 weeks must have elapsed since the completion of a
             non-nitrosourea containing chemotherapy regimen, and at least 6 weeks since the
             completion of a nitrosourea containing chemotherapy regimen; NOTE: For non-cytotoxic,
             FDA approved agents (i.e. celebrex, thalidomide, etc.) therapy could be started 2
             weeks after discontinuing this agent provided the patient has fully recovered from all
             toxicity associated with the agent; for investigational, non-cytotoxic agents a
             minimum of 3 weeks must have elapsed before the patient will be eligible for this
             study

          -  Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be
             able to care for himself/herself with occasional help from others)

          -  Absolute neutrophil count >= 1500/mm^3

          -  Platelets >= 100,000/mm^3

          -  Creatinine =< 1.5mg/dl

          -  Total Bilirubin =< 1.5mg/dl

          -  Transaminases =< 2.5 times above the upper limits of the institutional norm

          -  Patients must be able to provide written informed consent

          -  Women of childbearing potential must have a negative serum pregnancy test; the effects
             of AT-101 on the developing human fetus at the recommended therapeutic dose are
             unknown; for this reason and because Bcl-2 inhibitors have the potential to be
             teratogenic, women of child-bearing potential and men must agree to use adequate
             contraception (hormonal or barrier method of birth control; abstinence) prior to study
             entry and for the duration of study participation, and for at least one month
             following the last dose of AT-101; should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately

          -  Patients must have a Mini Mental State Exam score >= 15

        Exclusion Criteria:

          -  Patients with serious concurrent infection or medical illness which would jeopardize
             the ability of the patient to receive the treatment outlined in this protocol with
             reasonable safety; (Examples of medical illnesses are [but not limited to] the
             following: uncontrolled hypertension, symptomatic congestive heart failure, unstable
             angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that
             would limit compliance with study requirements)

          -  Patients who are pregnant or breast-feeding

          -  Patients who have received more than two prior treatments

          -  Patients who have been previously treated with gossypol, or have allergies to gossypol

          -  Patients receiving concurrent therapy for their tumor (i.e. chemotherapeutics or
             investigational agents); concurrent steroid use is allowed

          -  Patients with a concurrent malignancy are ineligible unless they are patients with
             curatively treated carcinoma-in-situ or basal cell carcinoma of the skin; patients
             with a prior malignancy are ineligible unless they have been free of disease for >=
             five years

          -  Patients with ≥ Grade 2 sensory neuropathy based on the NCI CTCAE

          -  Patients who are taking iron supplements

          -  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 pills are excluded

          -  Patients cannot be receiving cytochrome P450-inducing anticonvulsants (EIAEDs; e.g.,
             phenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine)

          -  Patients with malabsorption syndrome, disease significantly affecting gastrointestinal
             function, or resection of the stomach or small bowel are excluded; subjects with
             ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel
             obstruction are also excluded

          -  Eligibility of patients receiving any other medications or substances known to affect
             or with the potential to affect the activity or pharmacokinetics of AT-101 will be
             determined following review of their case by the Principal Investigator

          -  Patients with symptomatic hypercalcemia that is > Grade 2 (according to CTCAE)

          -  Requirement for routine use of hematopoietic growth factors (including granulocyte
             colony stimulating factor, granulocyte macrophage colony stimulating factor, or
             interleukin-11) or platelet transfusions to maintain absolute neutrophil counts or
             platelets counts above the required thresholds for study entry

          -  HIV-positive patients on combination antiretroviral therapy are ineligible because of
             the potential for pharmacokinetic interactions with AT-101; in addition, these
             patients are at increased risk of lethal infections when treated with
             marrow-suppressive therapy; appropriate studies will be undertaken in patients
             receiving combination antiretroviral therapy when indicated