Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

Clinical trial: EGFR Inhibition Using Weekly Erlotinib for Recurrent Malignant Gliomas

Summary: The purpose of this study is to test the effectiveness of a drug called erlotinib in treating the tumor. This is a multi-center pilot study that explores efficacy and molecular effects of high dose weekly erlotinib for recurrent EGFR vIII mutant malignant gliomas, and correlate molecular profile of pre-treatment tissue with outcome.

Detailed description: Amplification of the EGFR gene locus occurs also in approximately 40% of glioblastomas (GBM). Activating EGFR mutations such as EGFRvIII occur in approximately 50% of these GBMs (20% overall), leading to constitutive receptor activation and oncogenic signaling. The high frequency of EGFR signaling abnormalities in GBM led to initial enthusiasm for clinical trials of the EGFR TKIs erlotinib and gefitinib. However, responses were rare.

Eligibility: Inclusion Criteria:
  -  Histologically confirmed intracranial malignant glioma of the following types: Glioblastoma (GBM), Gliosarcoma (GS), Anaplastic astrocytoma (AA), Anaplastic oligodendroglioma (AO), Anaplastic oligoastrocytoma (AOA, also called anaplastic mixed gliomas or AMG), High grade glioma NOS (Not otherwise specified).
  -  EGFRvIII mutation detected on pretreatment tissue from at least 1 prior surgery.
  -  At least 15 unstained slides or at least 1 tissue blocks must be collected from at least one prior surgery.
  -  Recovered from toxic effects of prior therapies.
  -  Able to undergo contrast enhanced MRI scans (or CT scans for patients unable to tolerate MRI).
  -  Shown unequivocal evidence for contrast enhancing tumor progression by MRI (or CT for patients who cannot tolerate MRI) in comparison to a prior scan.
  -  Age > or = 18 years.
  -  Karnofsky Performance Status > or = 60%.
  -  Life expectancy of > 8 weeks.
  -  Normal organ and marrow function, adequate liver function and adequate renal function before starting therapy.
  -  Women of child-bearing potential and men must agree to use adequate contraception.
  -  Women of childbearing potential must have a negative pregnancy test documented within 7 days prior to treatment.
  -  Women must agree not to breast feed.
  -  Ability to understand and the willingness to sign a written informed consent document.
  -  Ability to swallow the tablets.
  Cohort A (medical) specific inclusion criteria:
  -  Fulfill all of the general inclusion criteria.
  -  MRI/CT must demonstrate measurable enhancing tumor of at least 1cm2 in cross-sectional area to allow assessment of radiographic response, unless: measurable disease is not present because the patient underwent gross total resection as the most recent anti-tumor therapy.
  -  At least 3 months have elapsed between any prior brain radiotherapy and initiation of study therapy.
  -  MRI/CT must demonstrate measureable enhancing tumor at least 1cm by 1cm squared in cross-sectional area to allow assessment of radiographic response.
  -  Stable or decreasing dose of corticosteroids for a minimum of 5 days before the baseline MRI/CT.
  -  The baseline MRI/CT must be performed on the 14th day or less prior to initiation of study treatment.
  Cohort B (surgical) specific inclusion criteria:
  -  Fulfill all of the general inclusion criteria.
  -  An MRI/CT scan showing progression is required.
  Exclusion Criteria:
  -  Received prior treatment with convection enhanced delivery, other catheter based intratumoral treatment, or carmustine (BCNU)/Gliadel wafers.
  -  Prior therapy that included stereotactic radiosurgery during therapy for newly diagnosed or recurrent disease, or re-irradiation of any type, must have confirmation of true progressive disease rather than radiation necrosis based upon surgical documentation of recurrent/progressive disease.
  -  Prior treatment with an EGFR inhibitor.
  -  Received prior treatment with direct VEGF/VEGFR inhibitors.
  -  Smoking or plan to smoke tobacco or marijuana during study therapy.
  -  Receiving any other investigational agents concurrently with study treatment.
  -  Taking Enzyme Inducing Anti-Epileptic Drug (EIAED). If previously on an EIAED, the patient must be off of it for at least two weeks prior to study treatment.
  -  History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib.
  -  Uncontrolled intercurrent illness that would limit compliance with study requirements.
  -  Have HIV and are receiving combination antiretroviral therapy.
  -  Other active concurrent malignancy.

Relevance to patient case: not relevant