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

NCT ID: NCT03632135

Last Updated: 2025-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-20
• Study Completion Date: 2023-12-31

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.

Conditions

Recurrent Glioblastoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

ChemoID assay

Intervention Type: DIAGNOSTIC_TEST

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.

Chemotherapy

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

ChemoID assay

Intervention Type: DIAGNOSTIC_TEST

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.

Chemotherapy

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DIAGNOSTIC_TEST

Chemotherapy

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

Intervention Type: DRUG

Other Intervention Names

Cytotoxic chemotherapy drugs

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cordgenics, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tulika Ranjan, MD

Role: PRINCIPAL_INVESTIGATOR

Allegheny Health Network

Locations

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

Maine Medical Center Research Institute

Scarborough, Maine, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

University of Cincinnati Cancer Institute

Cincinnati, Ohio, United States

Toledo University

Toledo, Ohio, United States

Providence Cancer Center Oncology

Portland, Oregon, United States

St. Luke's University Health Network

Bethlehem, Pennsylvania, United States

The Penn State Univeristy College of Medicine

Hershey, Pennsylvania, United States

Thomas Jefferson University Hospitals

Philadelphia, Pennsylvania, United States

Allegheny Health Network

Pittsburgh, Pennsylvania, United States

Charleston Area Medical Center

Charleston, West Virginia, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 28199863 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32197147 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 37287692 (View on PubMed)

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.

Reference Type: RESULT

PMID: 37137304 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

CG01GBM

Identifier Type: -

Identifier Source: org_study_id