18F-FDG PET and Osimertinib in Evaluating Glucose Utilization in Patients with EGFR Activated Recurrent Glioblastoma

Inclusion Criteria:

* Patients must be able to provide written informed consent
* Patients must have histologically proven World Health Organization (WHO) grade IV glioblastoma who have supratentorial contrast enhancing progressive or recurrent tumor by MRI imaging following standard or experimental treatment.
* Patients must have measurable contrast enhancing disease with a measurement of at least 1 x 1 x 1 cm using MRI contrast imaging
* Patients must have recovered from severe toxicity of prior therapy. The following intervals from previous treatments are required to be eligible:

  * 12 weeks from the completion of radiation
  * 6 weeks from a nitrosourea chemotherapy
  * 3 weeks from a non-nitrosourea chemotherapy
  * 4 weeks from any Food and Drug Administration (FDA) approved agents
  * 5 half-lives or 4 weeks, whichever is greater, from any investigational (not FDA-approved) agents
  * 4 weeks from the last treatment with bevacizumab
  * 2 weeks from administration of a non-cytotoxic, FDA-approved agent other than bevacizumab (e.g., hydroxychloroquine, etc.)
* Patient tumor sample must have evidence of EGFR activation as determined by EGFR amplification and/or EGFR mutations by fluorescent in situ hybridization (FISH) or sequencing approaches
* Patient tumor sample must not have p53 mutation

  * Note: Patients will be enrolled based on the documented EGFR/p53 status from the previous assays completed locally. If post enrollment evaluation of the archival tissue revealed that neither EGFR amplification nor EGFR mutations were present by using FISH or next generation sequencing, or mutant p53 by exon sequencing, the patients may continue their participation in the study. The investigator should discuss with patients regarding their willingness of continuation of participation in the study
* Patients must have a Karnofsky performance status (KPS) \>= 60
* Patients must have a life expectancy \>= 12 weeks
* Patients must be able to swallow medication by mouth
* Women of childbearing potential must have a negative serum pregnancy test prior to study entry. Women of childbearing 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. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

  * Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:

    * Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
    * Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for the institution
    * Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
* Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 4 months after completion of osimertinib administration
* Provision of informed consent for genetic research

Exclusion Criteria:

* Involvement in the planning and/or conduct of the study
* Previous enrollment in the present study or previous treatment with osimertinib
* Prior exposure to EGFR targeted therapy
* Currently receiving any other investigational agents
* Currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 weeks prior)
* Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment, with the exception of alopecia and grade 2, prior platinum-therapy? related neuropathy
* Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator?s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV)
* Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib
* Any of the following cardiac criteria:

  * Mean resting corrected QT interval (QTc) \> 470 msec obtained from an electrocardiogram (ECG), using the screening clinic ECG machine derived QTc value
  * Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block
  * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval
* Absolute neutrophil count \< 1.5 x 10\^9/L
* Platelet count \< 100 x 10\^9/L
* Hemoglobin \< 90 g/L
* Alanine aminotransferase \> 2.5 times upper limit of normal (ULN) if no demonstrable liver metastases or \> 5 times ULN in the presence of liver metastases
* Aspartate aminotransferase \> 2.5 times ULN if no demonstrable liver metastases or \> 5 times ULN in the presence of liver metastases
* Total bilirubin \> 1.5 times ULN if no liver metastases or \> 3 times ULN in the presence of documented Gilbert?s syndrome (unconjugated hyperbilirubinemia) or liver metastases
* Serum creatinine \> 1.5 times ULN concurrent with creatinine clearance \< 50 mL/min (measured or calculated by Cockcroft and Gault equation)?confirmation of creatinine clearance is only required when creatinine is \> 1.5 times ULN
* History of hypersensitivity active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib
* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
* Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements