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

NCT03632135 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: CG01GBM
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 13

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).

Conditions

Recurrent Glioblastoma

Keywords

ChemoID; Cancer stem cells; Drug response assay; Glioblastoma; Brain Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Median Progression Free Survival (PFS)

  36 months

Study Arms (2)

Physician Choice treatment

ACTIVE COMPARATOR

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; Drug: Chemotherapy

ChemoID-guided treatment

EXPERIMENTAL

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; Drug: Chemotherapy

Interventions

ChemoID assay 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.

ChemoID-guided treatment; Physician Choice treatment

Chemotherapy DRUG

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

Also known as: Cytotoxic chemotherapy drugs

ChemoID-guided treatment; Physician Choice treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Cordgenics, LLC: lead

Study Sites (13)

Kaiser Permanente

Los Angeles, California, 90027, United States

Location

Keck School of Medicine of the University of Southern California

Los Angeles, California, 90033, United States

Location

Louisiana State University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Maine Medical Center Research Institute

Scarborough, Maine, 04074, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

University of Cincinnati Cancer Institute

Cincinnati, Ohio, 45267, United States

Location

Toledo University

Toledo, Ohio, 43614, United States

Location

Providence Cancer Center Oncology

Portland, Oregon, 97225, United States

Location

St. Luke's University Health Network

Bethlehem, Pennsylvania, 18015, United States

Location

The Penn State Univeristy College of Medicine

Hershey, Pennsylvania, 17033, United States

Location

Thomas Jefferson University Hospitals

Philadelphia, Pennsylvania, 19104, United States

Location

Allegheny Health Network

Pittsburgh, Pennsylvania, 15212, United States

Location

Charleston Area Medical Center

Charleston, West Virginia, 25326, United States

Location

Related 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.

  PMID: 28199863 BACKGROUND

• 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.

  PMID: 32197147 BACKGROUND

• 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.

  PMID: 37287692 BACKGROUND

• 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.

  PMID: 37137304 RESULT

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Results Point of Contact

• Title: Pier Paolo Claudio, MD, Chief Scientific Officer
• Organization: Cordgenics

claudio@cordgenics.com

6064657226

Study Officials

• Tulika Ranjan, MD

  Allegheny Health Network

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: parallel group randomized controlled clinical trial

Study Record Dates

• First Submitted: August 13, 2018
• First Posted: August 15, 2018
• Study Start: May 20, 2018
• Primary Completion: June 16, 2022
• Study Completion: December 31, 2023
• Last Updated: April 15, 2025
• Results First Posted: November 30, 2023

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)