Recurrent Glioblastoma
Conditions
Keywords
ChemoID, Cancer stem cells, Drug response assay, Glioblastoma, Brain Cancer
Brief 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).
Detailed description
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.
Interventions
DIAGNOSTIC_TESTChemoID assay
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.
DRUGChemotherapy
Chemotherapies chosen by Physician or ChemoID assay are in the same list of FDA approved drugs to treat recurrent high-grade glioma
Sponsors
Cordgenics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
QUADRUPLE (Subject, Caregiver, 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.
Intervention model description
parallel group randomized controlled clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival (OS) | 36 months | Overall survival (OS) in recurrent GBM patients who have had a ChemoID assay-guided treatment compared to standard therapy chosen by the physician. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression Free Survival (PFS) | 36 months | Median Progression Free Survival in recurrent GBM patients who have had a ChemoID assay-guided treatment compared to standard therapy chosen by the physician. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Physician Choice Treatment Participants will be treated with standard-of-care chemotherapy chosen by the Physician from the provided list.
* 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.
ChemoID assay: The ChemoID test is a CLIA-certified and CAP-accredited drug response assay performed by a hospital clinical pathology laboratory that uses 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.
Chemotherapy: Chemotherapies chosen by Physician or ChemoID assay are in the same list of FDA approved drugs to treat recurrent Glioblastoma | 35 |
| ChemoID-guided Treatment Participants will be treated with ChemoID-guided standard-of-care chemotherapy drugs from the provided list.
* 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.
ChemoID assay: The ChemoID test is a CLIA-certified and CAP-accredited drug response assay performed by a hospital clinical pathology laboratory that uses 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.
Chemotherapy: Chemotherapies chosen by Physician or ChemoID assay are in the same list of FDA approved drugs to treat recurrent Glioblastoma | 43 |
| Total | 78 |
Baseline characteristics
| Characteristic | ChemoID-guided Treatment | Total | Physician Choice Treatment |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 38 Participants | 63 Participants | 25 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 15 Participants | 10 Participants |
| Age, Continuous | 61 years STANDARD_DEVIATION 13 | 59 years STANDARD_DEVIATION 12 | 55 years STANDARD_DEVIATION 11 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 36 Participants | 67 Participants | 31 Participants |
| Region of Enrollment United States | 43 participants | 78 participants | 35 participants |
| Sex: Female, Male Female | 15 Participants | 29 Participants | 14 Participants |
| Sex: Female, Male Male | 28 Participants | 49 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 35 / 35 | 43 / 43 |
| other Total, other adverse events | 6 / 35 | 5 / 43 |
| serious Total, serious adverse events | 12 / 35 | 18 / 43 |
Outcome results
Primary
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.
Time frame: 36 months
Population: Predetermined interim analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Physician Choice Treatment | Median Overall Survival (OS) | 7.5 months |
| ChemoID-guided Treatment | Median Overall Survival (OS) | 12 months |
Secondary
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.
Time frame: 36 months
Population: final analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Physician Choice Treatment | Median Progression Free Survival (PFS) | 3.5 months |
| ChemoID-guided Treatment | Median Progression Free Survival (PFS) | 10.1 months |