Our Approach to Glioblastoma Treatment
Currently, there are 11 active trials by the National Cancer Institute for glioblastoma, one of the most aggressive forms of brain cancer. The Cancer Research Life Foundation has proposed a groundbreaking trial with the agency that aims to treat patients with refractory glioblastoma who have failed other methods of care. In contrast with existing trials, the foundation believes that the Modified Multi Molecular Targeted Epigenetic Therapy (MTET) technology it is pursuing could be superior in many ways.
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The foremost superiority of MTET is its non-toxic nature. All current trials listed by the NCI have moderate to severe toxicity profiles ranging from inflammatory disease to death. MTET, sponsored by the foundation, is currently approved for glioblastoma as an orphan indication and has demonstrated extensive safety in both human and animal models, making it a potentially attractive method of treating glioblastoma—especially when other therapies fail. We look forward to treating patients with advanced brain cancer through phase II/III clinical trials with this superior technology.
Current National Cancer Institute Trials
Dose-Escalated Radiation Therapy Studies
Multiple trials are investigating whether higher doses of radiation can improve outcomes. One randomized phase II trial studies how well dose-escalated photon intensity-modulated radiation therapy (IMRT) or proton beam radiation therapy works compared with standard-dose radiation therapy when given with temozolomide in patients with newly diagnosed glioblastoma. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue, though it is not yet known whether dose-escalated approaches are more effective than standard-dose radiation therapy. This trial is being conducted at 158 locations nationwide.
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Another phase II trial examines whether an increased dose of radiation applied to a specific part of the brain works better than standard radiation therapy when given with temozolomide. The brain contains neural progenitor cells (NPC) that may contribute to tumor recurrence. Subventricular zone radiation therapy targeting these cells may improve local control and delay tumor recurrence. Conversely, a separate trial at the University of Maryland is studying low-dose whole-brain radiation therapy with temozolomide to determine if it can kill microscopic tumor cells outside the primary tumor area.
Chemotherapy and Targeted Drug Trials
Several trials are testing new drugs or drug combinations. A phase I trial studies the side effects and best dose of terameprocol in treating patients with high-grade glioma that has returned, conducted at 8 locations. Terameprocol works in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
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Another phase I trial examines adavosertib when given together with radiation therapy and temozolomide in patients with newly diagnosed or recurrent glioblastoma. Adavosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This combination therapy is being tested at 11 locations to determine if it works better than standard treatment.
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Mibefradil dihydrochloride is being studied at Yale University in combination with hypofractionated radiation therapy for progressive or recurrent glioblastoma. This drug may stop tumor cell growth by blocking necessary enzymes and may also make tumor cells more sensitive to radiation therapy. Similarly, nelfinavir mesylate is being tested at the University of Pennsylvania in combination with radiation and temozolomide to determine if this HIV medication can enhance cancer treatment by blocking enzymes needed for tumor cell growth.
Immunotherapy and Novel Approaches
A groundbreaking first-in-children phase I trial is using indoximod, an inhibitor of the immune checkpoint pathway indoleamine 2,3-dioxygenase (IDO), in combination with temozolomide-based therapy to treat pediatric brain tumors. This trial at 2 locations builds on preclinical glioblastoma models showing that adding IDO-blocking drugs to temozolomide plus radiation significantly enhanced survival by driving a vigorous, tumor-directed inflammatory response. The goal is to bring IDO-based immunotherapy into the clinic for children with brain tumors.
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At Wayne State University's Karmanos Cancer Institute, a phase I/II trial is studying epidermal growth factor receptor bispecific antibody (EGFRBi)-armed autologous T cells in patients with recurrent or refractory glioblastoma. These T cells, coated with antibodies, may have enhanced ability to seek out, attach to, and destroy glioblastoma cells by leveraging the body's own immune system.
Experimental Compounds
Several novel compounds are in early-stage testing. An open-label phase Ib clinical trial is evaluating intravenous administration of OKN-007 in patients with recurrent malignant glioma who have been previously treated with standard-of-care including surgical resection, radiation, chemotherapy, and in some cases investigational agents or bevacizumab (Avastin).
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Another trial is evaluating AQ4N in combination with radiotherapy and temozolomide in subjects with newly diagnosed glioblastoma multiforme. Phase 1b evaluates the safety and tolerability of AQ4N treatment at three different dose levels, while Phase 2a further evaluates safety, tolerability, and efficacy at a tolerated dose selected from Phase 1b.
The Need for Better Options
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Despite these numerous trials exploring various approaches—from dose-escalated radiation to immunotherapy to novel chemical compounds—all current options carry significant toxicity risks. The average cost of care for a refractory patient to live 12 months can reach $780,000 for a single drug alone, with hospitalizations and disability costs adding to the burden. The five-year survival rate for glioblastoma remains less than 4 percent, underscoring the urgent need for safer, more effective treatment options like MTET that the Cancer Research Life Foundation is working to bring to patients.For more information on current glioblastoma clinical trials, visit the National Cancer Institute at cancer.gov/about-cancer/treatment/clinical-trials/adult-glioblastoma.