A Study of PD 0332991 in Patients With Recurrent Rb Positive Glioblastoma
Condition: Glioblastoma; Gliosarcoma; Anaplastic Astrocytoma
MeSH terms: Glioblastoma; Astrocytoma; Gliosarcoma
Intervention: PD 0332991 (pre-surgery); PD 0332991; Resection as clinical care
Intervention description: PD 0332991 for 7 days prior to an indicated, intended surgical resection for progression; PD 0332991 daily for 21 consecutive days followed by a 7 day break off therapy, repeating cycles; Indicated, intended, surgical resection as clinical care
Intervention MeSH terms: Palbociclib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Glioblastoma; Gliosarcoma; Anaplastic astrocytoma; Malignant astrocytoma NOS; Malignant glioma; GBM

Summary:

      This study will determine the efficacy of the small molecule CDK4/6 inhibitor PD 0332991 (as
      measured by progression free survival at 6 months) in patients with recurrent glioblastoma
      multiforme or gliosarcoma who are Rb positive. A total of 30 patients will be treated; 15
      will undergo a planned surgical resection and receive drug for 7 days prior to surgery,
      followed by drug after recovery from surgery, and the other 15 patients will receive drug
      without a planned surgical procedure.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients 18 years or older with KPS > 60, with life expectancy of > 8 weeks with
             radiographically proven recurrent, intracranial Glioblastoma multiforme or
             Gliosarcoma; patients must have documentation of Rb positive disease.

          -  All patients must sign an informed consent and must have signed an authorization for
             the release of their protected health information.

          -  Patients must have had prior external beam radiation and temozolomide chemotherapy;
             there is no limit to the number of prior chemotherapies used; patients may be treated
             in their first, second or third relapse

          -  Patients must have recovered from the toxic effects of prior therapy

          -  Patients must have adequate bone marrow function and renal function before starting
             therapy. A pre-study EKG with a normal QT interval is required for all patients

          -  Patients must have shown unequivocal evidence for tumor progression by MRI scan and on
             a steroid dose that has been stable for at least 7 days.

          -  Patients must have an interval of greater than or equal to 42 days from the completion
             of radiation therapy to study entry.

          -  A subset of 15 patients will be enrolled prior to a planned, indicated surgical
             resection. Patients can be enrolled pre-operatively only if they are surgical
             candidates, do not have evidence of an acute intracranial hemorrhage and are able to
             start protocol treatment in a window of 7 days before surgery.

          -  Male and female patients with reproductive potential must use an approved
             contraceptive method. Women of childbearing potential must have a negative beta-HCG
             pregnancy test

          -  Blocks or slides of tumor tissue from a previous surgery must be available to do IHC
             Rb staining. Patients with negative tumors (Rb negative) will be excluded from the
             study.

        Exclusion Criteria:

          -  Patients must not have any significant medical illnesses that in the investigator's
             opinion cannot be adequately controlled with appropriate therapy or would compromise
             the patient's ability to tolerate this therapy.

          -  Patients with a history of any other cancer (except non-melanoma skin cancer or
             carcinoma in-situ of the cervix), unless in complete remission and off of all therapy
             for that disease for a minimum of 3 years are ineligible.

          -  Patients on enzyme-inducing anti-epileptic drugs or other drugs that cause CYP3A
             enzyme induction or inhibition will not be eligible