Clinical trial NCT03632135: 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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Recurrent Glioblastoma
Keywords: ChemoID
Cancer stem cells
Drug response assay
Glioblastoma
Brain Cancer
Lead sponsor: Cordgenics, LLC
Sponsor class: INDUSTRY
First posted: 2018-08-15
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: parallel group randomized controlled clinical trial
Primary purpose: DIAGNOSTIC

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.

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.

Primary outcomes:
measure: Median Overall Survival (OS)
timeFrame: 36 months
Secondary outcomes:
measure: Median Progression Free Survival (PFS)
timeFrame: 36 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine of the University of Southern California
state: California
city: New Orleans
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Scarborough
country: United States
facility: Maine Medical Center Research Institute
state: Maine
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Institute
state: Ohio
city: Toledo
country: United States
facility: Toledo University
state: Ohio
city: Portland
country: United States
facility: Providence Cancer Center Oncology
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's University Health Network
state: Pennsylvania
city: Hershey
country: United States
facility: The Penn State Univeristy College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospitals
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Area Medical Center
state: West Virginia
Study officials:
affiliation: Allegheny Health Network
name: Tulika Ranjan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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, 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.