ChemoID-Guided Therapy for Glioblastoma

(CSCRGBM Trial)

Recruiting at 13 trial locations

Overseen By Sara Ohm, BS

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Cordgenics, LLC

Disqualifiers: Newly diagnosed GBM, Pregnancy, Renal insufficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 36 months

78 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, the use of herbal preparations or tetrahydrocannabinol/cannabidiol is strongly discouraged, but not completely prohibited.

What data supports the effectiveness of the ChemoID-guided treatment for glioblastoma?

A study involving 40 patients with recurrent glioblastoma showed that using a cancer stem cell assay to guide chemotherapy, like ChemoID, can improve treatment outcomes by targeting cancer stem cells, which are often resistant to standard chemotherapy. ^{1 2 3 4 5}

Is ChemoID-guided therapy for glioblastoma safe for humans?

The study on ChemoID-guided therapy for glioblastoma does not provide specific safety data, but related chemotherapy treatments like temozolomide have shown mostly mild to moderate side effects, such as nausea and vomiting, which are generally manageable. ^{2 6 7 8 9}

What makes ChemoID-guided chemotherapy unique for treating glioblastoma?

ChemoID-guided chemotherapy is unique because it uses a personalized approach to identify the most effective chemotherapy for each patient by targeting cancer stem cells, which are often resistant to standard treatments. This method improves survival rates by tailoring therapy to the individual's tumor characteristics, unlike traditional one-size-fits-all approaches. ^{2 10 11 12 13}

What is the purpose of this trial?

This trial tests if using the ChemoID test to choose chemotherapy drugs can improve outcomes for patients with recurrent glioblastoma (GBM) compared to standard treatments chosen by doctors. The ChemoID test has been evaluated for its effectiveness in selecting personalized chemotherapy for GBM patients.

Research Team

Tulika Ranjan, MD

Principal Investigator

Allegheny Health Network

Eligibility Criteria

This trial is for adults with confirmed recurrent glioblastoma who can undergo surgery and have certain blood counts within normal ranges. They must not be pregnant, nursing, or have severe kidney issues, and should agree to use contraception if applicable. Those with other recent cancers or using the OPTUNE device are excluded.

Inclusion Criteria

Informed consent obtained and signed

In all cases, the diagnosis must be confirmed by a pathologist

Prior to surgery there was imaging evidence of measurable progressive disease (PD)

Exclusion Criteria

Severe or chronic renal insufficiency (creatinine clearance ≤ 30 ml/min)

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

Abnormal hematological results at inclusion with: Neutrophils < 1,500/mm3; Blood-platelets < 100,000/mm3

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive chemotherapy treatment based on either standard-of-care chosen by the physician or guided by ChemoID assay results

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ChemoID assay
• Chemotherapy

Trial Overview The study tests whether a cancer stem cell test called ChemoID can predict how well patients respond to chemotherapy in recurrent glioblastoma. Participants will receive standard chemotherapy guided by the results of this test.

Participant Groups

Group I: ChemoID-guided treatment Experimental Treatment 2 Interventions

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 II: Physician Choice treatment Active Control 2 Interventions

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.

Chemotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in United States as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Canada as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Japan as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in China as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Switzerland as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Who Is Running the Clinical Trial?

Cordgenics, LLC

Lead Sponsor

Trials

3

Recruited

230+

Findings from Research

Temozolomide, a key chemotherapy drug for glioblastoma, faces significant resistance primarily due to the activation of the O-6-methylguanine-DNA methyltransferase enzyme, which repairs the DNA damage caused by the drug, thus restoring genomic integrity.

Recent research has identified various mechanisms contributing to temozolomide resistance, including indirect DNA repair systems, drug efflux mechanisms, epigenetic changes, and influences from the tumor microenvironment, highlighting the complexity of overcoming this resistance in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide Resistance: A Multifarious Review on Mechanisms Beyond O-6-Methylguanine-DNA Methyltransferase. Rao, V., Kumar, G., Vibhavari, RJA., et al.[2023]

Malignant gliomas are challenging to treat, with surgery and radiation providing the most significant survival benefits, while chemotherapy offers only modest improvements.

The paper discusses the limited effectiveness of current chemotherapy agents and suggests that future treatments may rely on combination therapies that include both targeted biological compounds and traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in the treatment of malignant gliomas. Stern, JI., Raizer, JJ.[2007]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Chemosensitivity of glioma cells in vitro: a meta analysis. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Treatment of unmethylated MGMT-promoter recurrent glioblastoma with cancer stem cell assay-guided chemotherapy and the impact on patients' healthcare costs. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Insights into pharmacotherapy of malignant glioma in adults. [2018]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Temozolomide Resistance: A Multifarious Review on Mechanisms Beyond O-6-Methylguanine-DNA Methyltransferase. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Chemotherapy in the treatment of malignant gliomas. [2007]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Toxicity profile of temozolomide in the treatment of 300 malignant glioma patients in Korea. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Adherence to antiemetic guidelines in patients with malignant glioma: a quality improvement project to translate evidence into practice. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Palonosetron for the prevention of chemotherapy-induced nausea and vomiting in glioblastoma patients treated with temozolomide: a phase II study. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Phase II study to evaluate the safety and efficacy of intravenous palonosetron (PAL) in primary malignant glioma (MG) patients receiving standard radiotherapy (RT) and concomitant temozolomide (TMZ). [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Cancer stem cell assay-guided chemotherapy improves survival of patients with recurrent glioblastoma in a randomized trial. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Intratumoral chemotherapy. [2007]

12. United States pubmed.ncbi.nlm.nih.gov

Interstitial chemotherapy for malignant glioma: Future prospects in the era of multimodal therapy. [2023]

13. United States pubmed.ncbi.nlm.nih.gov

Analysis of Chemopredictive Assay for Targeting Cancer Stem Cells in Glioblastoma Patients. [2020]