Patient case: 82-year-old male with glioma; genetic feature: BRAF

Clinical trial: Vaccine Therapy in Treating Patients Undergoing Surgery for Recurrent Glioblastoma Multiforme

Summary: RATIONALE: Vaccines made from a person's tumor cells and dendritic cells may help the body build an effective immune response to kill tumor cells.
  PURPOSE: This phase I trial is studying the side effects of vaccine therapy in treating patients undergoing surgery for recurrent glioblastoma multiforme (GBM).

Detailed description: OBJECTIVES:
  Primary
  -  To evaluate the feasibility and safety of an autologous brain tumor stem cell messenger ribonucleic acid (mRNA)-loaded dendritic cell vaccine in adult patients with recurrent glioblastoma multiforme.
  Secondary
  -  To assess humoral and cellular immune responses to vaccination.
  -  To compare the proportion of vaccinated patients alive at 6 months from the time of surgery for recurrent tumor with matched historical cohorts.
  OUTLINE: Patients undergo surgical resection of tumor. Tumor tissue samples are collected to isolate brain tumor stem cells (BTSCs) and for extraction and amplification of BTSC-specific mRNA. Within 4 weeks after surgical resection, patients undergo leukapheresis over 4 hours to generate dendritic cells (DCs). Patients also undergo leukapheresis at 1 week after the third vaccination and then at least every 3 months as needed for generation of additional DCs.
  Patients receive autologous BTSC mRNA-loaded DC vaccine intradermally once weekly for 3 weeks and then once monthly in the absence of disease progression or unacceptable toxicity.
  After completion of study treatment, patients are followed periodically.

Eligibility: Inclusion Criteria:
  -  Age >18 years of age
  -  First recurrence of GBM (WHO Grade IV glioma or astrocytoma) in surgically accessible areas with prior histologic diagnosis of GBM
  -  No known contraindications to receiving Avastin
  -  Karnofsky Performance Status (KPS) of > 70%
  -  Radiation Therapy (RT) with ≥ 45 Gy tumor dose, completed ≥ 8 weeks prior to study entry
  Exclusion Criteria:
  -  Contrast-enhancing tumor component crossing the midline, multi-focal tumor, or tumor dissemination (subependymal or leptomeningeal)
  -  Clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment
  -  Pregnant or need to breast feed during the study period (Negative beta-human chorionic gonadotropin (HCG) test required), or unable to maintain use of contraception while on study
  -  Active infection requiring treatment or an unexplained febrile (> 101.5 degrees F) illness
  -  Known immunosuppressive disease, autoimmune disease or human immunodeficiency virus infection, Hepatitis B or Hepatitis C
  -  Unstable or severe intercurrent medical conditions such as severe heart (New York Association Class 3 or 4) or lung (FEV1 < 50%) disease, uncontrolled diabetes mellitus
  -  Prior brachytherapy, carmustine wafer therapy, radiolabeled monoclonal antibodies, or stereotactic radiosurgery
  -  Prior inguinal lymph node dissection
  Avastin-Specific Exclusion Criteria
  Subjects meeting any of the following criteria are ineligible for study entry:
  -  Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg)
  -  Prior history of hypertensive crisis or hypertensive encephalopathy
  -  New York Heart Association (NYHA) Grade II or greater congestive heart failure
  -  History of myocardial infarction or unstable angina within 6 months prior to enrollment
  -  History of stroke or transient ischemic attack within 6 months prior to enrollment
  -  Significant vascular disease (e.g. aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) (within 6 months prior to enrollment)
  -  History of hemoptysis (> or = 1/2 teaspoon of bright red blood per episode) within 28 days prior to enrollment
  -  Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
  -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment
  -  Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to enrollment
  -  Serious, non-healing wound, active ulcer or untreated bone fracture
  -  Proteinuria as defined by > +1 on urinalysis dipstick
  -  Known hypersensitivity to any component of Avastin
  -  Pregnant (positive pregnancy test) or lactation

Relevance to patient case: not relevant