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

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.

Inclusion criteria

• 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;
• Informed consent obtained and signed;
• Willing and able to commit to study procedures including long-term follow-up visit(s);
• Histopathologically confirmed 2016-WHO grade III recurrent glioma, and grade IV recurrent glioblastoma (GBM), inclusive of Gliosarcoma
• In all cases, the diagnosis must be confirmed by a pathologist.
• Recurrent surgically resectable tumor and/or biopsy;
• 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;
• Prior to surgery there was imaging evidence of measurable progressive disease (PD);
• Start of radiotherapy, if indicated, must occur at least 2 weeks after surgery and/or biopsy;
• Estimated survival of at least 3 months;
• 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;
• If indicated radiation therapy and chemotherapy must start within 8 weeks of tumor resection or biopsy.
• 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;
• The use of herbal preparation or tetrahydrocannabinol/cannabidiol is strongly discouraged, but not contraindicated;

Exclusion criteria

• Subjects with newly diagnosed GBM
• 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;
• Abnormal hematological results at inclusion with: Neutrophils < 1,500/mm3; Blood-platelets < 100,000/mm3
• Severe or chronic renal insufficiency (creatinine clearance ≤ 30 ml/min);
• Patient unable to follow procedures, visits, examinations described in the study;
• Any usual formal indication against imaging examinations (important claustrophobia, pacemaker);
• 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;
• OPTUNE device is not permitted in the study;
• Patients cannot participate to any clinical trials utilizing a liquid biomarker or imaging studies that impact the overall survival.