This current study will use a new treatment approach based on each patient's tumor genomic profiling consisting of whole genome sequencing, exome analysis, and RNA sequencing as well as predictive modeling. This new treatment strategy has shown promising results in adult patients with other solid tumors.

Patients with recurrent glioblastoma who are candidates for surgery for their clinical management will have tumor tissue taken at the time of surgery. Tissue samples will be obtained from the contrasting edge as well as infiltrating margins. Circulating tumor DNA will also be taken from blood samples before, and after surgery and every 2 months. Genomic profiling of the tumor tissue will be performed and a Molecular Tumor Board will review the profiling within 28 to 35 days of surgery. If specific potential targets are amenable to treatment, a treatment recommendation will be made. Up to 4 drugs could be suggested to the treating physician. The patient and the treating physician may or may not choose to use the recommendation. Any drug from the US Pharmacopeia may be chosen. If the treatment as suggested is given, patients will be followed for toxicity and efficacy, including progression and survival. If the treatment is not given, patients will be followed for progression and survival.

Inclusion Criteria:

• Patients must understand and provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization prior to initiation of any study-specific procedures
• Have a life expectancy of at least 3 months
• Patients must have a diagnosis of histologically confirmed Glioblastoma that is felt on imaging to be progressive despite standard of care treatment
• at least 18 years of age
• Patient is a good medical candidate for a standard of care surgical procedure
• Patients may enroll independent of number of prior therapies, but must have received prior radiation therapy
• Patients must have a performance status (KPS) of at least 60.

Exclusion Criteria:

• Uncontrolled concurrent illness including psychiatric illness, or situations that would limit compliance with the study requirements or the ability to willingly give written informed consent

Eligibility for treatment using the specialized Tumor Board recommendations

• Patients must have fully recovered from any toxicity associated with surgery
• Must begin treatment no longer than 35 calendar days from surgery
• Must have KPS at least 60
• Must have Absolute Neutrophil Count (ANC) at least 1500/mm3, platelets at least 125,000/mm2, Hg at least 8 gm/dl
• Must have electrolytes (Na, K, Co2, Cl) within normal limits using institutional guidelines
• Must have baseline MRI within 14 days prior to starting cycle 1, day 1 of treatment (+/- 3 days)
• Additional laboratory guidelines will be based upon therapies suggested by the specialized Tumor Board based upon anticipated, known toxicities of those agents and must be within at least 1.5 x upper normal limits of institutional normal limits
• Patient must agree to follow the recommended treatment regimen, including clinic visits, laboratory, imaging, and toxicity assessments

Patients presenting with recurrent or progressive glioblastoma that are eligible for surgical resection.