Personalized Drug Regimens for Glioblastoma

Overseen By Charles S Cobbs, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Swedish Medical Center

Disqualifiers: Metastatic disease, Hypertension, Myocardial infarction, Stroke, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

10 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial involves new drug regimens, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators for specific guidance.

What data supports the effectiveness of the combination drug therapy for glioblastoma?

Research shows that using a combination of drugs, like gefitinib and GSK461364A, in specially designed nanoparticles can work better together to kill glioma cells than using each drug alone. This approach helps the drugs work together more effectively and reduces side effects, offering hope for better treatment outcomes in aggressive brain cancers like glioblastoma. ^{1 2 3 4 5}

Is combination drug therapy for glioblastoma generally safe for humans?

The research does not provide specific safety data for combination drug therapy in humans, but it suggests that combining drugs can improve treatment responses and reduce side effects compared to single drug treatments. ^{1 3 6 7 8}

How is the combination drug therapy for glioblastoma different from other treatments?

The combination drug therapy for glioblastoma is unique because it uses a personalized approach to select drug combinations that can overcome chemotherapy resistance and target the diverse cell populations within the tumor, potentially improving treatment efficacy compared to standard treatments. ^{1 3 9 10 11}

What is the purpose of this trial?

Proposed treatment of subjects with newly diagnosed glioblastoma with novel personalized drug regimens identified to be effective in vitro using cancer stem cells derived from their individual tumors, alongside standard of care radiation and TMZ.

Research Team

Charles S Cobbs

Principal Investigator

Ivy Center for Advanced Brain Tumor Treatment

Eligibility Criteria

This trial is for adults over 18 with a recent diagnosis of Glioblastoma (GBM, WHO grade 4) who haven't had cancer treatment before. They should be healthy enough for surgery to remove most of the tumor and have a life expectancy over 6 months. Participants need good blood counts, no HIV or Hepatitis B/C, and must be physically able to handle daily activities.

Inclusion Criteria

Patients must be negative for HIV, Hepatitis B and C

Patients must have a life expectancy of >6 months

Baseline hematologic studies and chemistry and coagulation profiles must meet specific criteria: Hemoglobin (Hgb)> 8 g/dL, Absolute Neutrophil Count (ANC) > 1,000/mm3, Platelet count > 100,000/mm3, Creatinine < 2 mg/dL, Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) < 3x upper limit of normal (ULN)

Exclusion Criteria

Serious intercurrent medical illness

I have not had a heart attack or unstable chest pain in the last 6 months.

My cancer has spread to other parts of my body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a personalized combination of up to 3 FDA approved drugs alongside standard of care chemoradiation with TMZ

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long-term follow-up

Participants are monitored for overall survival

36 months

Treatment Details

Interventions

• Combination Drug Therapy

Trial Overview The study tests personalized drug combinations (up to three FDA-approved drugs) tailored using cancer stem cells from each patient's tumor. These are given alongside standard radiation and TMZ chemotherapy treatments for newly diagnosed glioblastoma.

Participant Groups

Group I: Personalized Combination Drug Therapy for Cancer Stem Cells Experimental Treatment 1 Intervention

Administer combinations of up to 3 FDA approved drugs from a panel of compounds selected based on high throughput screening

Who Is Running the Clinical Trial?

Swedish Medical Center

Lead Sponsor

Trials

55

Recruited

8,500+

Findings from Research

The study developed a nanoparticle-based combination therapy using gefitinib and GSK461364A, which showed enhanced effectiveness against glioblastoma cells compared to single drug treatments and other combinations.

Optimal ratios of the two drugs in PLGA-PEG nanoparticles significantly reduced the clonogenic potential of glioma cells, indicating a synergistic effect that could improve treatment outcomes for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic Action of Gefitinib and GSK41364A Simultaneously Loaded in Ratiometrically-Engineered Polymeric Nanoparticles for Glioblastoma Multiforme. Velpurisiva, P., Rai, P.[2020]

Temozolomide has been shown to improve survival in adults with newly diagnosed glioblastoma, particularly in patients with tumors that have MGMT promoter methylation, marking a significant advancement in the treatment of malignant gliomas.

Current research is focused on identifying patient subsets that will benefit from chemotherapy and developing strategies to overcome drug resistance, aiming to enhance the effectiveness of existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy of High-Grade Astrocytomas in Adults. Puduvalli, VK., Hoang, N.[2018]

Glioblastoma, the most aggressive brain cancer, has a poor prognosis with an average survival of less than 15 months despite standard treatments like surgery, radiotherapy, and chemotherapy.

The WINDOW Consortium aims to develop effective therapies by addressing both the chemotherapy resistance of glioblastoma cells and the tumor's heterogeneous nature, focusing on drug combinations that penetrate the blood-brain barrier and target diverse cell populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

WINDOW consortium: A path towards increased therapy efficacy against glioblastoma. Abdul, KU., Houweling, M., Svensson, F., et al.[2019]

Combined therapeutic strategies for glioblastoma multiforme (GBM) show superior efficacy compared to single therapies, addressing the challenges of drug resistance and high recurrence rates associated with this aggressive brain tumor.

The review highlights the importance of co-therapeutic agents, timing, and delivery systems in optimizing treatment outcomes for GBM, suggesting that advancements in nanotechnology could enhance the effectiveness of these combined therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined-therapeutic strategies synergistically potentiate glioblastoma multiforme treatment via nanotechnology. Yang, J., Shi, Z., Liu, R., et al.[2021]

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]

Glioma stem cells (GSCs) are crucial in glioblastoma (GBM) for tumor growth and resistance to treatments, highlighting the need for effective combination therapies.

The study presents a straightforward workflow for high-throughput screening of drug combinations that can potentially enhance treatment efficacy against GSCs in GBM, which could lead to better therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells. Hu, Z., Zhou, T., Wu, F., et al.[2021]

Glioblastoma (GBM) is a highly resistant cancer, particularly due to the survival of cancer stem cells (GSCs) that evade treatment with temozolomide (TMZ) by enhancing DNA repair and avoiding cell death.

The review suggests that combining multiple drugs with targeted nanotechnology could improve treatment outcomes by specifically attacking GSCs, as single-drug therapies have not significantly improved patient prognosis in over 15 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapeutics and drug-delivery approaches in the modulation of glioblastoma stem cell resistance. Smiley, SB., Zarrinmayeh, H., Das, SK., et al.[2022]

Glioblastoma is a challenging brain tumor with poor 5-year survival rates, highlighting the urgent need for new treatment options.

Existing medications used for other diseases may have anticancer properties that could significantly improve survival for glioblastoma patients, suggesting a potential new approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repurposing some older drugs that cross the blood-brain barrier and have potential anticancer activity to provide new treatment options for glioblastoma. Rundle-Thiele, D., Head, R., Cosgrove, L., et al.[2021]

Spirohydantoin mustard (spiromustine) is a promising therapy for glioblastoma multiforme that effectively penetrates the blood-brain barrier and targets brain tumors, potentially improving treatment outcomes.

Intracarotid administration of cisplatin enhances drug delivery directly to the tumor while minimizing systemic exposure, indicating a strategic approach to chemotherapy for better efficacy and safety in treating this aggressive brain cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spiromustine and intracarotid artery cisplatin in the treatment of glioblastoma multiforme. Resio, MJ., DeVroom, HL.[2019]

A new computerized framework using deep reinforcement learning has been developed to create personalized chemo-radiation therapy regimens for glioblastoma multiforme (GBM) patients, potentially improving treatment outcomes compared to conventional methods.

The deep Q network (DQN) model outperformed traditional Q learning in designing treatment protocols, showing robustness against variations in tumor size and treatment duration, suggesting it could lead to more effective personalized therapies for GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep neural networks for neuro-oncology: Towards patient individualized design of chemo-radiation therapy for Glioblastoma patients. Ebrahimi Zade, A., Shahabi Haghighi, S., Soltani, M.[2022]

The SynergySeq platform successfully identifies potential drug combinations for glioblastoma (GBM) treatment by analyzing gene expression data from GBM samples and drug response data from the LINCS database.

This approach allows for the development of patient-specific targeted therapies that could enhance treatment efficacy for GBM, which currently has a median survival of only 14 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug and disease signature integration identifies synergistic combinations in glioblastoma. Stathias, V., Jermakowicz, AM., Maloof, ME., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Synergistic Action of Gefitinib and GSK41364A Simultaneously Loaded in Ratiometrically-Engineered Polymeric Nanoparticles for Glioblastoma Multiforme. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Chemotherapy of High-Grade Astrocytomas in Adults. [2018]

3. Scotland pubmed.ncbi.nlm.nih.gov

WINDOW consortium: A path towards increased therapy efficacy against glioblastoma. [2019]

4. Australia pubmed.ncbi.nlm.nih.gov

Combined-therapeutic strategies synergistically potentiate glioblastoma multiforme treatment via nanotechnology. [2021]

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

Chemotherapy in the treatment of malignant gliomas. [2007]

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

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Novel therapeutics and drug-delivery approaches in the modulation of glioblastoma stem cell resistance. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Repurposing some older drugs that cross the blood-brain barrier and have potential anticancer activity to provide new treatment options for glioblastoma. [2021]

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

Spiromustine and intracarotid artery cisplatin in the treatment of glioblastoma multiforme. [2019]

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

Deep neural networks for neuro-oncology: Towards patient individualized design of chemo-radiation therapy for Glioblastoma patients. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Drug and disease signature integration identifies synergistic combinations in glioblastoma. [2021]