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

Recurrent Glioblastoma Clinical Trial

— CSCRGBM  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03632135
• Other study ID #: CG01GBM
• Status: Completed
• Phase: Phase 3
• Start date: May 20, 2018
• Est. completion date: December 31, 2023

Study information

• Verified date: January 2024
• Source: Cordgenics, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: December 31, 2023
• Est. primary completion date: June 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma
• Recurrence
• Recurrent Glioblastoma

Intervention

Diagnostic Test:
• ChemoID 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.

Drug:
• Chemotherapy
Chemotherapies chosen by Physician or ChemoID assay are in the same list of FDA approved drugs to treat recurrent high-grade glioma

Locations

Country	Name	City	State
United States	St. Luke's University Health Network	Bethlehem	Pennsylvania
United States	Charleston Area Medical Center	Charleston	West Virginia
United States	University of Cincinnati Cancer Institute	Cincinnati	Ohio
United States	The Penn State Univeristy College of Medicine	Hershey	Pennsylvania
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Kaiser Permanente	Los Angeles	California
United States	Keck School of Medicine of the University of Southern California	Los Angeles	California
United States	Louisiana State University Health Sciences Center	New Orleans	Louisiana
United States	Thomas Jefferson University Hospitals	Philadelphia	Pennsylvania
United States	Allegheny Health Network	Pittsburgh	Pennsylvania
United States	Providence Cancer Center Oncology	Portland	Oregon
United States	Maine Medical Center Research Institute	Scarborough	Maine
United States	Toledo University	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Cordgenics, LLC

Country where clinical trial is conducted

United States, 

References & Publications (4)

Howard CM, Valluri J, Alberico A, Julien T, Mazagri R, Marsh R, Alastair H, Cortese A, Griswold M, Wang W, Denning K, Brown L, Claudio PP. Analysis of Chemopredictive Assay for Targeting Cancer Stem Cells in Glioblastoma Patients. Transl Oncol. 2017 Apr;10(2):241-254. doi: 10.1016/j.tranon.2017.01.008. Epub 2017 Feb 12. — View Citation

Ranjan T, Howard CM, Yu A, Xu L, Aziz K, Jho D, Leonardo J, Hameed MA, Karlovits SM, Wegner RE, Fuhrer R, Lirette ST, Denning KL, Valluri J, Claudio PP. Cancer Stem Cell Chemotherapeutics Assay for Prospective Treatment of Recurrent Glioblastoma and Progressive Anaplastic Glioma: A Single-Institution Case Series. Transl Oncol. 2020 Apr;13(4):100755. doi: 10.1016/j.tranon.2020.100755. Epub 2020 Mar 17. — View Citation

Ranjan T, Sengupta S, Glantz MJ, Green RM, Yu A, Aregawi D, Chaudhary R, Chen R, Zuccarello M, Lu-Emerson C, Moulding HD, Belman N, Glass J, Mammoser A, Anderson M, Valluri J, Marko N, Schroeder J, Jubelirer S, Chow F, Claudio PP, Alberico AM, Lirette ST, — View Citation

Ranjan T, Yu A, Elhamdani S, Howard CM, Lirette ST, Denning KL, Valluri J, Claudio PP. Treatment of unmethylated MGMT-promoter recurrent glioblastoma with cancer stem cell assay-guided chemotherapy and the impact on patients' healthcare costs. Neurooncol Adv. 2023 May 12;5(1):vdad055. doi: 10.1093/noajnl/vdad055. eCollection 2023 Jan-Dec. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	36 months
Secondary	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
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.	36 months
Secondary	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
Secondary	Objective Tumor Response	Objective tumor response measured by RANO (Response Assessment in Neuro-oncology Criteria)	36 months
Secondary	Quality of Life Questionnaire	Health-Related Quality of Life questionnaire (HRQOL)	36 months