A Study of PX-866 in Patients With Glioblastoma Multiforme at Time of First Relapse or Progression
Condition: Glioblastoma
MeSH terms: Glioblastoma
Intervention: PX-866
Intervention description: 1 cycle = 8 weeks on study PX-866 - 8mg PO Daily
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to find out whether the new drug PX-866 will slow the growth of
      your glioblastoma multiforme.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed diagnosis of glioblastoma multiforme
             (GBM), with recurrent or progressive disease following or during primary treatment not
             curable with standard therapies.

          -  All patients must have formalin fixed paraffin embedded tissue available for
             translational studies.

          -  Presence of bidimensionally measurable enhancing lesions on CT or MRI, with at least
             one lesion with a minimum dimension of 1 cm x 1 cm (i.e. both dimensions must be ≥ 1.0
             cm). Baseline CT or MRI must be done within 14 days prior to registration.

          -  ECOG performance of 0, 1 or 2.

          -  Age ≥ 18 years of age. Previous Therapy

        Chemotherapy:

        Patients may have received prior adjuvant chemotherapy and/or concurrent chemoradiation as
        part of primary therapy, but must have received no therapy for recurrent/ progressive GBM
        (i.e. PX-866 must be first treatment for recurrence/ progression). A minimum of 28 days
        since the last dose of chemotherapy must have elapsed prior to registration.

        Targeted Therapy:

        No prior therapy with a phosphatidylinositol 3-kinase (PI-3K) inhibitor. Other targeted
        agents are permissible provided they were given as part of front line treatment. A minimum
        of 56 days (8 weeks) must have elapsed since last day for anti-angiogenic therapy and
        minimum of 28 days for other targeted agents.

        Radiation:

        Patients may have had prior radiation therapy provided at least 28 days have elapsed from
        the day of the last fraction of radiation to the date of registration.

        - Previous Surgery: Previous surgery is permitted provided that wound healing has occurred
        and at least 14 days have elapsed prior to registration.

        5.1.7 Laboratory Requirements (must be done within 7 days prior to registration)

        Hematology:

        Granulocytes (AGC) ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L

        Chemistry:

        Serum creatinine ≤ 1.5 x UNL Total bilirubin ≤ 1.5 x UNL ALT and AST ≤ 1.5 x UNL Glucose ≤
        8.9 mmol/L (≤ Grade 1)

          -  Women must be post menopausal, surgically sterile or use a reliable form of
             contraception while on study and for 30 days after discontinuing therapy. Women of
             childbearing potential must have a pregnancy test taken and proven negative within 7
             days prior to registration and must not be lactating.

          -  Patient consent must be obtained according to local Institutional and/or University
             Human Experimentation Committee requirements. It will be the responsibility of the
             local participating investigators to obtain the necessary local clearance, and to
             indicate in writing to the NCIC CTG Study Coordinator that such clearance has been
             obtained, before the trial can commence in that centre. Because of differing
             requirements, a standard consent form for the trial will not be provided but a sample
             form is provided. A copy of the initial full board REB approval and approved consent
             form must be sent to the central office. The patient must sign the consent form prior
             to registration (exception for translations). Please note that the consent form for
             this study must contain a statement which gives permission for the NCIC CTG and
             monitoring agencies to review patient records Patients who cannot give informed
             consent (i.e. mentally incompetent patients, or those physically incapacitated such as
             comatose patients) are not to be recruited into the study. Patients competent but
             physically unable to sign the consent form may have the document signed by their
             nearest relative or legal guardian. Each patient will be provided with a full
             explanation of the study before consent is requested.

          -  Patients must be accessible for treatment and follow-up. Patients registered on this
             trial must be treated and followed at the participating centre. This implies there
             must be reasonable geographical limits (for example: 2 hour's driving distance) placed
             on patients being considered for this trial. Investigators must assure themselves that
             the patients registered on this trial will be available for complete documentation of
             the treatment, adverse events, response assessment and follow-up.

          -  In accordance with NCIC CTG policy, protocol treatment is to begin within 2 working
             days of patient registration.

        Exclusion Criteria:

          -  Patients who have other active malignancies (i.e. documented by imaging, clinical exam
             or marker) are to be excluded. (Please call NCIC CTG if any questions about the
             interpretation of this criterion).

          -  Known HIV-positive patients.

          -  Uncontrolled diabetes mellitus.

          -  Patients should be on a stable dose of steroid (i.e. no change in dose for 2 weeks
             prior to registration) when entered on study. Patients recently started on steroids or
             whose steroid dose was increased in the recent past should not be started on protocol
             treatment until at least 2 weeks have passed from the time of steroid dose increment
             or initiation. Under these circumstances, baseline CT or MRI scan for purposes of
             assessment of response to protocol treatment should be done at the time of initiation
             of protocol therapy (i.e., these patients must be re-imaged to control for steroid
             effects).

        Note:

        The idea behind this is to restrict entry to a subset of patients who are not rapidly
        changing: especially rapidly deteriorating. If a patient being worked up for the trial
        appears to need to have steroid introduced or increased, the patient should be treated as
        is medically appropriate (i.e., have the steroid introduced or increased). Steroid should
        NOT be withheld if clinically indicated just so that patients can be registered on study!

          -  Patients with upper gastrointestinal or other conditions that would preclude
             compliance or absorption of oral medication are not eligible.

          -  Patients with active or uncontrolled infections, or with serious illnesses or medical
             conditions which would not permit the patient to be managed according to the protocol.

          -  Patients are not eligible if they have a known hypersensitivity to the study drugs or
             their components.

          -  Patients who have had prior treatment with a PI3 kinase inhibitor.