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

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

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).

Study Overview

• Status: Completed
• Conditions: Recurrent Glioblastoma
• Intervention / Treatment: Diagnostic test: ChemoID assay; Drug: Chemotherapy

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.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente
    • Los Angeles, California, United States, 90033
      • Keck School of Medicine of the University of Southern California
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health Sciences Center
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Medical Center Research Institute
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Cancer Institute
    • Toledo, Ohio, United States, 43614
      • Toledo University
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence Cancer Center Oncology
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's University Health Network
    • Hershey, Pennsylvania, United States, 17033
      • The Penn State Univeristy College of Medicine
    • Philadelphia, Pennsylvania, United States, 19104
      • Thomas Jefferson University Hospitals
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Health Network
  • West Virginia
    • Charleston, West Virginia, United States, 25326
      • Charleston Area Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Physician Choice treatment; 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; 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; Other Names: Cytotoxic chemotherapy drugs
Experimental: ChemoID-guided treatment; 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; 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; Other Names: Cytotoxic chemotherapy drugs

What is the study measuring?

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
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
Objective Tumor Response	Objective tumor response measured by RANO (Response Assessment in Neuro-oncology Criteria)	36 months
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
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
Quality of Life Questionnaire	Health-Related Quality of Life questionnaire (HRQOL)	36 months

Collaborators and Investigators

• Sponsor: Cordgenics, LLC
• Investigators: Principal Investigator: Tulika Ranjan, MD, Allegheny Health Network

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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, Denning KL, Howard CM. Cancer stem cell assay-guided chemotherapy improves survival of patients with recurrent glioblastoma in a randomized trial. Cell Rep Med. 2023 May 16;4(5):101025. doi: 10.1016/j.xcrm.2023.101025. Epub 2023 May 2.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2018
• Primary Completion (Actual): June 16, 2022
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: August 13, 2018
• First Submitted That Met QC Criteria: August 13, 2018
• First Posted (Actual): August 15, 2018

Study Record Updates

• Last Update Posted (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Glioblastoma; Brain Cancer; Cancer stem cells; ChemoID; Drug response assay
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence
• Other Study ID Numbers: CG01GBM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No