standard chemotherapy vs. chemotherapy guided by cancer stem cell test in recurrent glioblastoma

Conditions: Recurrent Glioblastoma

Summary: the purpose of this clinical study is to confirm the utility of chemosensitivity tumor testing on cancer stem cells (chemoid) as a predictor of clinical response in poor prognosis malignant brain tumors such as recurrent glioblastoma (gbm).

this study is designed as a parallel group randomized controlled clinical trial to determine if recurrent glioblastoma (gbm) patients treated with drugs predicted by the chemoid assay will have better outcomes than patients treated with standard-of-care control therapy chosen by the physician. upon obtaining informed consent, all eligible participants affected by recurrent gbm will have a tumor biopsy to undergo chemoid drug response testing with multiple fda-approved chemotherapeutic agents. eligible participants will be randomized to a standard treatment arm with control treatment (chemotherapy chosen by the physician from a provided list), or to a study arm of fda-approved drugs selected by the chemoid drug response assay.

Eligibility criteria:
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.

Keywords: chemoid cancer stem cells drug response assay glioblastoma brain cancer