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Ivy Blog

Robust Glioblastoma Clinical Trials Program Offers Brain Cancer Patients New Treatment Options

Next year, an estimated 25,930 people in the United States and over 308,000 people worldwide will be diagnosed with a primary malignant brain tumor (CBTRUS). Glioblastoma multiforme (GBM) is the most common primary brain cancer in adults and the standard of care to treat this disease only postpones tumor progression. Most patients with glioblastoma experience a tumor recurrence just months after their first surgery to remove the tumor. Because these tumors almost always come back after the first-line treatment and a second line hasn’t been established, the average five-year survival rate of patients with glioblastoma is less than 5%. 

Drug development for brain cancer lags behind in comparison to other types of cancers with larger patient populations. Only 5% of new investigational drug applications submitted to the FDA for cancer therapies are successful, and for brain cancer the rate of success is closer to 1% over the past two decades.  

Temozolomide is the only effective chemotherapy available for high-grade glioma patients, but conventional treatment alone is not sufficient to prevent tumor regrowth. Clinical trials are the most effective method to research and develop new therapeutics for glioblastoma and other brain cancers. 

Hope for Glioblastoma Patients

“Our goal at the Ivy Brain Tumor Center is to discover new drug agents that deliver results to patients as quickly as possible, and we do this through our innovative Phase 0 clinical trials program. We’re committed to improving the prognosis of patients with malignant brain tumors and our dedicated team is with them every step of the way,” said Nader Sanai, MD, director of the Ivy Brain Tumor Center and director of neurosurgical oncology at Barrow Neurological Institute.

The lack of new treatment options for aggressive brain tumors requires a bold approach to rapidly identify new, effective therapies that will increase life expectancy and contribute to a cure. 

The Ivy Brain Tumor Center is the largest Phase 0 clinical trials program in the world, with six active clinical trials and additional studies scheduled to open later this year.

“The progress achieved by the Ivy Center’s Phase 0 clinical trials program has surpassed anything I have seen in the 16 years I have been funding brain cancer research. Our mission is to discover and develop a new FDA-approved therapy for brain cancer,” says Catherine Ivy, president and founder of the Ben & Catherine Ivy Foundation.

Keep reading to learn more about the Ivy Center’s targeted portfolio of treatment options for patients with glioblastoma and other brain tumors. 

Active Clinical Trials for Recurrent and Newly-Diagnosed Glioma and Meningioma

Sonodynamic Therapy – Recurrent high-grade glioma

Sonodynamic therapy (SDT) is a potential new treatment modality for patients with brain cancer. In this first-in-human Phase 0/1 clinical trial for patients with recurrent high-grade gliomas, the drug agent SONALA-001 is administered to the patient intravenously just days before a planned resection to remove their tumor. This nontoxic drug selectively accumulates in the glioma cells. A device called Exablate 4000 Type-2 is then fixed to the patient’s skull to receive magnetic resonance-guided focused ultrasound (MRgFUS) technology. The drug is activated upon delivery of low-dose focused ultrasound targeting only the tumor cells.

The initial results were presented at the ESMO Congress and indicated that SDT rapidly leads to targeted oxidative stress and cell death in human glioblastoma tissue. SDT was well-tolerated in all patients.

Industry collaborators SonALAsense and Insightec; 30 participants; National Clinical Trial number: NCT04559685.


Infigratinib – Recurrent high-grade glioma

The Phase 0/2 clinical trial of infigratinib, an FGFR1-3 selective tyrosine kinase inhibitor, is for patients with recurrent high-grade gliomas with alterations in FGFR (fibroblast growth factor receptor) gene, which have been shown to be oncogenic/promote tumor growth. During the screening process, the Ivy Center will test the patient’s tumor tissue for the FGFR-TACC3 fusion gene or mutations in FGFR1 and FGFR3 genes. Only patients with tumors that have these fusions or mutations are eligible for this study.

Industry collaborator BridgeBio Pharma, Inc. affiliate company QED Therapeutics, Inc.; 20 participants; National Clinical Trial number: NCT04424966.


Ribociclib – Preoperative glioma and meningioma

The Phase 0 clinical trial of ribociclib, an FDA-approved drug for advanced breast cancer, is part of a new class of targeted therapies that undermines cancer cell division and could form the backbone of a new drug cocktail for patients with malignant brain tumors. The initial results demonstrate ribociclib is uniquely capable of breaking through the blood-brain barrier and effectively reaching its molecular target in cancer cells. This study also discovered a potential mechanism in the tumor of drug resistance and the Ivy Center is now investigating drug combinations to undermine the resistance.

Drug company Novartis; 48 participants; National Clinical Trial number: NCT02933736.


Ribociclib plus Everolimus – Recurrent high-grade glioma

The Ivy Brain Tumor Center has been investigating ribociclib as a monotherapy and working to identify a potent combined-drug regimen to undermine a resistance mechanism of ribociclib in brain tumors. The Phase 0/2 study of ribociclib in combination with everolimus is designed for recurrent high-grade glioblastoma patients scheduled for resection.

Results from this study were published in the journal of Neuro-oncology and demonstrated ribociclib achieved pharmacologically relevant concentrations in gadolinium (Gd)-non-enhancing tumor, consistent with the observed tumor pharmacodynamics (PD) effects; while everolimus demonstrated minimal penetration in the (Gd)-non-enhancing compartment of the tumor.

This study is available to patients across multiple sites throughout the Phoenix Metropolitan Area including Barrow Neurological Institute, HonorHealth Research Institute at HonorHealth Scottsdale Osborn Medical Center and Dignity Health Chandler Regional Hospital and Medical Center.

Drug company Novartis; 24 participants. National Clinical Trial number: NCT03834740.


Pamiparib – Newly diagnosed or recurrent glioblastoma

The Phase 0/2 clinical trial of pamiparib, an oral investigational small molecule PARP inhibitor, is designed for patients with newly diagnosed and recurrent glioblastoma. PARP is a protein that plays an important role in cell survival response to DNA damage. Patients demonstrating a positive PK- and PD- response may advance to an expansion phase of the study to take pamiparib therapeutically with fractionated radiotherapy.

A New Drug Application (NDA) for pamiparib for patients with ovarian cancer has been accepted and granted priority by Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more lines of chemotherapy.

Industry collaborator BeiGene; 30 participants; National Clinical Trial number: NCT04614909.


Abemaciclib and LY3214996 – Recurrent glioblastoma

The Ivy Brain Tumor Center published the initial results of the Phase 0/2 clinical trial of abemaciclib, a CDK4/6 inhibitor; and LY3214996, a ERK inhibitor; in the ASCO Meeting Library. The combined targeted therapies demonstrated positive PK- and PD- response in tumor cells. The Ivy Center continues to accrue patients for this trial.

Industry collaborator Eli Lilly; 50 participants; National Clinical Trial number: NCT04391595.


Upcoming Clinical Trials for Glioblastoma

Niraparib – Newly diagnosed glioblastoma and recurrent glioma (grades II-IV)

The Phase 0 study of niraparib, (ZEJULA), an oral poly (ADP-ribose) polymerase (PARP) inhibitor from GSK, is designed for patients with newly diagnosed glioblastoma (GBM) and recurrent glioma (grades II-IV). The study is in partnership with UCSF Medical Center, who was instrumental in designing the PD assay for Arm B and will also accrue patients for Arm B. The Ivy Center will evaluate up to 42 participants subdivided into two arms: Arm A for newly diagnosed glioblastoma patients and Arm B for recurrent grade II-IV gliomas patients.

Last year the FDA approved niraparib as a monotherapy maintenance treatment for adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy, regardless of biomarker status.

Industry collaborator GSK and academic collaborator UCSF Medical Center; 42 participants; National Clinical Trial Number: Coming Soon


AZD1390 – Recurrent glioblastoma

The open-label Phase 0/1b study of AZD1390, an ATM inhibitor, is designed for recurrent glioblastoma patients requiring re-radiation therapy. The study is subdivided into Arm A to determine the optimal time interval (OTI) and the dose-escalation Arm B. The Ivy Center will initially recruit patients in Arm A only; the timing of when Arm B will open is contingent on results from a separate active phase 1 clinical trial, NCT03423628.

AZD1390 is a potent brain penetrant ATM (Ataxia telangiectasia mutant) kinase inhibitor that blocks ATM-dependent signaling and repair of DNA double strand breaks (DSBs) in the genome. AZD1390 therefore is being explored in combination with irradiation, which induces DSBs. ATM inhibition may also generate an exploitable DNA damage response (DDR) dependency against tumor cells with other DDR pathway defects.

Industry collaborator AstraZeneca; at least 21 participants; National Clinical Trial Number: Coming Soon


The Ivy Brain Tumor Center’s clinical trials are funded by the Ben and Catherine Ivy Foundation and the individual donors of the Barrow Neurological Foundation.

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