Standard Chemotherapy vs. Chemotherapy Guided by Cancer Stem Cell Test in Recurrent Glioblastoma

Inclusion Criteria:

1. Men and Women and members of all ethnic groups who are at least 18 years old at the time of enrollment are eligible for this trial;
2. Informed consent obtained and signed;
3. Willing and able to commit to study procedures including long-term follow-up visit(s);
4. Histopathologically confirmed 2016-WHO grade III recurrent glioma, and grade IV recurrent glioblastoma (GBM), inclusive of Gliosarcoma
5. In all cases, the diagnosis must be confirmed by a pathologist.
6. Recurrent surgically resectable tumor and/or biopsy;
7. Participants who have undergone surgical resection should have received an MRI or a scan after surgery in order to visualize residual tumor. If not, the operative report must be available;
8. Prior to surgery there was imaging evidence of measurable progressive disease (PD);
9. Start of radiotherapy, if indicated, must occur at least 2 weeks after surgery and/or biopsy;
10. Estimated survival of at least 3 months;
11. Hgb \> 9 gm; absolute neutrophil count (ANC) \> 1500/μl; platelets \> 100,000; Creatinine \< 1.5 times the upper limit of laboratory normal value; Bilirubin \< 2 times the upper limit of laboratory normal value; serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) \< 3 times the upper limit of laboratory normal value;
12. If indicated radiation therapy and chemotherapy must start within 8 weeks of tumor resection or biopsy.
13. Bevacizumab (Avastin) is allowed. If indicated it should be initiated at least 4 weeks post craniotomy or biopsy if the wound has healed well without any drainage or cellulitis;
14. The use of herbal preparation or tetrahydrocannabinol/cannabidiol is strongly discouraged, but not contraindicated;

Exclusion Criteria:

1. Subjects with newly diagnosed GBM
2. Pregnant women or nursing mothers cannot participate in the study. Women of childbearing age must have a negative pregnancy test within 72 hours prior to study entry. Women of childbearing potential must practice medically approved contraceptive precautions;
3. Abnormal hematological results at inclusion with: Neutrophils \< 1,500/mm3; Blood-platelets \< 100,000/mm3
4. Severe or chronic renal insufficiency (creatinine clearance ≤ 30 ml/min);
5. Patient unable to follow procedures, visits, examinations described in the study;
6. Any usual formal indication against imaging examinations (important claustrophobia, pacemaker);
7. History of another malignancy in the previous 2 years, with a disease-free interval of \< 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer, any time prior to screening, are eligible;
8. OPTUNE device is not permitted in the study;
9. Patients cannot participate to any clinical trials utilizing a liquid biomarker or imaging studies that impact the overall survival.