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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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Standard Chemotherapy Versus Chemotherapy Chosen by Cancer Stem Cell Chemosensitivity Testing in the Management of Patients With Recurrent Glioblastoma Multiforme (GBM).

Conditions
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Recurrent Glioblastoma

Intervention / Treatment
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* Diagnostic Test: ChemoID assay
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: parallel group randomized controlled clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Physician Choice treatment<br>Participants will be treated with control chemotherapy treatment (standard-of-care chemotherapy chosen by the Physician from the provided list). Control chemotherapy treatment will be chosen from any of the following standard-of-care chemotherapy drugs or combinations: Carboplatin; Irinotecan; Etoposide; BCNU; CCNU; Temozolomide; Procarbazine; Vincristine; Imatinib; Procarbazine, CCNU, Vincristine; Carboplatin, Irinotecan; Carboplatin, Etoposide; Temozolomide, Etoposide; Temozolomide, Imatinib. The treating physician will NOT receive the ChemoID assay results from the ChemoID lab. | Diagnostic Test: ChemoID assay<br>* 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.<br>Drug: Chemotherapy<br>* Chemotherapies chosen by Physician or ChemoID assay are in the same list of FDA approved drugs to treat recurrent high-grade glioma<br>* Other names: Cytotoxic chemotherapy drugs;|
| Experimental: ChemoID-guided treatment<br>Participants will be treated with ChemoID-guided standard-of-care chemotherapy drugs from the provided list. ChemoID-guided treatment will be chosen from the following standard-of-care chemotherapy drugs or combinations: Carboplatin; Irinotecan; Etoposide; BCNU; CCNU; Temozolomide; Procarbazine; Vincristine; Imatinib; Procarbazine, CCNU, Vincristine; Carboplatin, Irinotecan; Carboplatin, Etoposide; Temozolomide, Etoposide; Temozolomide, Imatinib. The treating physician will receive the ChemoID assay results from the ChemoID lab. | Diagnostic Test: ChemoID assay<br>* 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.<br>Drug: Chemotherapy<br>* Chemotherapies chosen by Physician or ChemoID assay are in the same list of FDA approved drugs to treat recurrent high-grade glioma<br>* Other names: Cytotoxic chemotherapy drugs;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Overall Survival (OS) | Overall survival (OS) in recurrent GBM patients who have had a ChemoID assay-guided treatment compared to standard therapy chosen by the physician. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival at 6, 9, and 12 Months (OS6mo, OS9mo, OS12mo) | Overall survival at 6, 9, and 12 months in recurrent GBM patients who have had a ChemoID assay-guided treatment compared to standard therapy chosen by the physician. | 6, 9, and 12 months | 
| Median Progression Free Survival (PFS) | Median Progression Free Survival in recurrent GBM patients who have had a ChemoID assay-guided treatment compared to standard therapy chosen by the physician. | 36 months | 
| Progression Free Survival at 4, 6, 9, and 12 Months (PFS4mo, PFS6mo, PFS9mo, PFS12mo) | Progression Free survival at 4, 6, 9, and12 months in recurrent GBM patients who have had a ChemoID assay-guided treatment compared to standard therapy chosen by the physician. | 4, 6, 9, and 12 months | 
| Objective Tumor Response | Objective tumor response measured by RANO (Response Assessment in Neuro-oncology Criteria) | 36 months | 
| Quality of Life Questionnaire | Health-Related Quality of Life questionnaire (HRQOL) | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ChemoID, Cancer stem cells, Drug response assay, Glioblastoma, Brain Cancer