Standard Chemotherapy vs. Chemotherapy Guided by Cancer Stem Cell Test in Recurrent Glioblastoma
Condition: Recurrent Glioblastoma
MeSH terms: Glioblastoma; Recurrence
Intervention: ChemoID assay; Chemotherapy
Intervention description: The ChemoID test is a CLIA-certified and CAP-accredited drug response assay performed by a hospital clinical pathology laboratory that uses a patient's live tumor cells to indicate which chemotherapy agent (or combinations) will kill not only bulk of tumor cells, but importantly the cancer stem cells (CSCs) that are known to cause cancer to recur. During the assay, cancer stem cells and bulk tumor cells from an individual patient are exposed to FDA-approved chemotherapy drugs.
The test measures the cytotoxic effect of actual doses of standard-of-care chemotherapies. The ChemoID drug response assay reports a prioritized list of effective and ineffective chemotherapies. The test is designed to target cancer stem cells to mitigate tumor relapse.; Chemotherapies chosen by Physician or ChemoID assay are in the same list of FDA approved drugs to treat recurrent high-grade glioma
Phase: Phase 3
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: parallel group randomized controlled clinical trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Study investigators will be kept blind to the schedule. All participants will be screened by the ChemoID drug response assay; however, the treating physician will receive the ChemoID results only for those participants who are randomized to ChemoID-guided treatment arm.
Enrollment: 78.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ChemoID; Cancer stem cells; Drug response assay; Glioblastoma; Brain Cancer

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).
    

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.