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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to treating glioblastoma, a type of brain cancer, using personalized drug combinations (Combination Drug Therapy). The drugs are selected based on their effectiveness against cancer cells from each person's tumor, alongside standard treatments like radiation and a drug called TMZ. The trial seeks participants who have been newly diagnosed with glioblastoma and have not yet received any other cancer treatments. Participants should also have a tumor that can be surgically removed and expect to live at least six more months. The trial aims to discover a more effective treatment plan tailored to each patient. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining drugs might be promising for treating glioblastoma, a type of brain cancer. In studies with mice, these drug combinations extended their lifespan and reduced tumor size. This suggests that using multiple drugs together might be more effective than using just one.

However, it is crucial to observe how people respond to these treatments. Past studies reported side effects such as high blood sugar, skin rashes, and mouth sores. These side effects are common with many cancer treatments and can vary among individuals.

This trial is in its earliest phase, meaning the treatment is still being tested for safety in humans. Early trials focus on ensuring the treatment does not cause serious harm. The drugs in this study have already received FDA approval for other uses, indicating a known level of safety. However, because this is a new combination, careful monitoring remains essential. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard care for glioblastoma, which typically involves surgery, radiation, and chemotherapy with drugs like temozolomide, this new treatment uses a personalized combination drug therapy. Researchers are excited because it targets cancer stem cells specifically, using up to three FDA-approved drugs chosen through high throughput screening. This approach offers a tailored tactic, potentially improving effectiveness by directly addressing the unique characteristics of each patient’s tumor, which is not something current treatments can do.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

Research has shown that using a personalized combination of drugs for treating glioblastoma appears promising. Early results found that in 5 out of 5 patients with recurring glioblastoma, the disease was completely controlled, with some patients nearly achieving a full response. This trial will evaluate a personalized combination drug therapy approach, where participants receive combinations of up to 3 FDA-approved drugs selected through high throughput screening. Studies have demonstrated that combining treatments can be more effective than using a single drug, enhancing their effectiveness against glioblastoma. In one study, using a combination of treatments significantly increased survival time compared to using just one drug. This method is believed to be effective because it attacks the cancer in several ways, potentially shrinking tumors and extending survival. ^{1 2 3 4 6}

Who Is on the Research Team?

Charles S Cobbs

Principal Investigator

Ivy Center for Advanced Brain Tumor Treatment

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. immunitybio.com immunitybio.com/initial-data-shows100-disease-control-in-5-out-of-5-patients-with-recurrent-glioblastoma-with-two-patients-in-near-complete-response-treated-with-immunitybios-anktiva-nk-cell-therapy-p/

Initial Data Shows 100% Disease Control in 5 Out of 5 ... Initial Data Shows 100% Disease Control in 5 Out of 5 Patients With Recurrent Glioblastoma With Two Patients in Near Complete Response Treated ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7053190/

Combined-therapeutic strategies synergistically potentiate ... The combined therapies demonstrate superior results than those of single therapies against GBM. The co-therapeutic agents, the timing of therapeutic strategies ...

3. massgeneralbrigham.org massgeneralbrigham.org/en/about/newsroom/articles/combination-therapy-overcoming-treatment-resistance-in-glioblastoma

Research Spotlight: Combination Therapy Shows Promise ... When we gave this drug to mouse models of GBM alongside anti-PD1 therapy, the results were promising—the tumors shrank, the mice lived ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/adtp.202300197

Combination Drug Therapy of Glioblastoma: Lessons from ... When TTF was combined with TMZ chemotherapy, a significant increase in overall survival (20.9 months vs 16 months) compared to TMZ alone was ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6191404/

Combination therapy to checkmate Glioblastoma: clinical ... This approach, also referred to as combination therapy, shows synergistic effects in terms of drug efficacy and is by far the most effective ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0753332224010217

The effects of the combination therapy of chemotherapy ... The study found a mean OS of 15.7 months and a mean PFS of 8.4 months (range 6.6–10.2). The most frequent side events were hyperglycemia, rash, oral mucositis, ...