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

• ClinicalTrials.gov Identifier: NCT03632135
• Recruitment Status: Active, not recruiting
• First Posted: August 15, 2018
• Last Update Posted: February 15, 2022
• Sponsor: Cordgenics, LLC
• Information provided by (Responsible Party): Cordgenics, LLC

Tracking Information

• First Submitted Date: August 13, 2018
• First Posted Date: August 15, 2018
• Last Update Posted Date: February 15, 2022
• Actual Study Start Date: May 15, 2018
• Estimated Primary Completion Date: June 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 13, 2018)

Median Overall Survival (OS) [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 14, 2018)

• Overall Survival at 6, 9, and 12 months (OS6mo, OS9mo, OS12mo) [ Time Frame: 6, 9, and 12 months ]
  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.
• Median Progression Free Survival (PFS) [ Time Frame: 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.
• Progression Free Survival at 4, 6, 9, and 12 months (PFS4mo, PFS6mo, PFS9mo, PFS12mo) [ Time Frame: 4, 6, 9, and 12 months ]
  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.
• Objective Tumor Response [ Time Frame: 36 months ]
  Objective tumor response measured by RANO (Response Assessment in Neuro-oncology Criteria)
• Quality of life questionnaire [ Time Frame: 36 months ]
  Health-Related Quality of Life questionnaire (HRQOL)

Original Secondary Outcome Measures (submitted: August 13, 2018)

• Overall Survival at 6, 9, and 12 months (OS6mo, OS9mo, OS12mo) [ Time Frame: 6, 9, and 12 months ]
  Overall survival at 6, 9, and 12 months (OS6mo, OS9mo, OS12mo) in recurrent GBM patients who have had a ChemoID assay-guided treatment compared to standard therapy chosen by the physician.
• Median Progression Free Survival (PFS) [ Time Frame: 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.
• Progression Free Survival at 4, 6, 9, and 12 months (PFS4mo, PFS6mo, PFS9mo, PFS12mo) [ Time Frame: 4, 6, 9, and 12 months ]
  Progression Free survival at 4, 6, 9, and12 months (PFS4mo, PFS6mo, PFS9mo, PFS12mo) in recurrent GBM patients who have had a ChemoID assay-guided treatment compared to standard therapy chosen by the physician.
• Objective Tumor Response [ Time Frame: 36 months ]
  Objective tumor response measured by RANO (Response Assessment in Neuro-oncology Criteria)
• HRQOL [ Time Frame: 36 months ]
  Health-Related Quality of Life (HRQOL)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Standard Chemotherapy vs. Chemotherapy Guided by Cancer Stem Cell Test in Recurrent Glioblastoma
• Official Title: Standard Chemotherapy Versus Chemotherapy Chosen by Cancer Stem Cell Chemosensitivity Testing in the Management of Patients With Recurrent Glioblastoma Multiforme (GBM).
• 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.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

parallel group randomized controlled clinical trial

Masking: Quadruple (Participant, Care Provider, 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.

Primary Purpose: Diagnostic

• Condition: 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 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 ovarian cancer
  Other Name: Cytotoxic chemotherapy drugs

Study Arms

• 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.
  Interventions:

  • Diagnostic Test: ChemoID assay
  • Drug: Chemotherapy
• 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.

  Interventions:

  • Diagnostic Test: ChemoID assay
  • Drug: Chemotherapy

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.
• Tulika Ranjan, Candace M. Howard, Jagan Valluri, Alexander Yu, Khaled Aziz, David Jho, Terrence Julien, Jody Leonardo, Anthony Alberico, Antonio Cortese, Krista Denning, and Pier Paolo Claudio. Prospective Analysis of Cancer Stem Cell Drug Response Assay for Glioblastoma Patients. J Clin Oncol 36, 2018 (suppl; abstr 2057) - ASCO Annual Meeting, Chicago, June 1-5, 2018.
• Pier Paolo Claudio, Sarah E Mathis, Rounak Nande, Anthony Alberico, Walter Neto, Logan Lawrence, James Denvir, Gerrit A. Kimmey, Aneel A. Chowdhary, Maria R. B. Tria Tirona, Mark Jeffrey Mogul, Terrence D Julien, Rida S Mazagri, Gerald Oakley, Krista L Denning, Thomas Dougherty, Linda Brown, and Jagan Valluri. Novel chemosensitivity assay for targeting cancer stem-like cells in brain tumors. Journal of Clinical Oncology 2014 32:15_suppl, e13012-e13012
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: October 16, 2021): 150
• Original Estimated Enrollment (submitted: August 13, 2018): 300
• Estimated Study Completion Date: December 31, 2022
• Estimated Primary Completion Date: June 30, 2022 (Final data collection date for primary outcome measure)

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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03632135
• Other Study ID Numbers: CG01GBM
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Cordgenics, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Cordgenics, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Tulika Ranjan, MD; Allegheny Health Network

• PRS Account: Cordgenics, LLC
• Verification Date: October 2021