Open Trials

In this research study, we want to learn more about the effects of the study drug larotrectinib on children with brain tumors. We want to learn how well it works to shrink brain tumors when used alone or when given with standard chemotherapy or after radiation therapy.

The investigators are asking people to be in this research study who have been diagnosed with a high-grade glioma with a certain abnormal gene called NTRK. The investigators will evaluate the disease of the patients after they take the larotrectinib for 2 cycles. After taking the study drug for 2 cycles, the investigators will determine the next course of treatment. Patients will continue to receive either larotrectinib alone, larotrectinib with standard chemotherapy or larotrectinib alone after radiation therapy. The length of treatment depends on how well the patient is doing and which standard treatment the doctor thinks is best for them.

There is also a surgical cohort of the study where tumor samples and blood samples will be collected and sent to researchers to determine if larotrectinib is found in the tumor and how much is in the blood.

The purpose of this study is to learn about the effects of the study drug tocilizumab in patients with Adamantinomatous craniopharyngioma (ACP). We think this drug can benefit ACP patients who may or may not have undergone surgery or radiation as it may help shrink this type of brain tumor or slow its growth.

We are asking individuals to be in this research study if they have been diagnosed with ACP that has increased in size or is unable to be removed entirely by surgery.

Tocilizumab is a form of targeted immunosuppressive therapy and is given as a liquid through an intravenous (IV) infusion once every 2 weeks. The drug is approved by the United States Food and Drug administration (FDA) for a different disease in children.

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The purpose of this phase 2 study is to see if a cancer vaccine (PEP-CMV) can help patients’ immune system fight against high-grade glioma and medulloblastoma. We think PEP-CMV, which is an immunotherapy given as an injection into the thigh, can benefit children by training their immune system to seek out and attack these tumors.

This study is designed for patients with diffuse intrinsic pontine glioma (DIPG) or malignant glioma (WHO grade 3 or 4) who are newly diagnosed (within 6 weeks of finishing radiation) or patients with medulloblastoma whose tumor has come back at any point after having received radiation. Patients on this study receive a single, 5-day course of oral chemotherapy called temozolomide, which is deigned to condition the immune system, followed by PEP-CMV injections every 2 weeks for 3 vaccines, then monthly.

In this research study, we want to find out if the study drug Lutathera is effective in treating different kinds of brain cancer. We also want to find the safest dose of this drug that does not cause serious side effects.

We are asking the participation of children and young adults who have been diagnosed with either a high-grade brain or spine tumor or a meningioma that expresses a specific protein called somatostatin receptor on its surface. This is confirmed with a special type of scan called a DOTATATE PET.

Lutathera is a form of targeted radiation therapy and is given by intravenous (IV) infusion once every 2 months. This drug is approved by the FDA (Food and Drug Administration) for the treatment of another type of cancer but it has not yet been approved for the treatment of brain/spine tumors.

The purpose of this study is to learn more about the effects of the study drug binimetinib in patients with Adamantinomatous craniopharyngioma (ACP). We think this drug can benefit ACP patients who may or may not have undergone surgery or radiation as it may help shrink this type of brain tumor or slow its growth. This is based on laboratory studies on cells grown in the lab from craniopharyngioma tumor tissue collected from patients at surgery.

We are asking individuals to be in this research study if they have been diagnosed with ACP that has increased in size or is unable to be removed entirely by surgery.

Binimetinib is a form of targeted chemotherapy and is given orally as a tablet twice a day. This drug is approved by the United States Food and Drug administration (FDA) to treat a different disease in children and adults.

TarGeT is an innovative multi-arm clinical trial offering a precision medicine approach to treat children, adolescents, and young adults newly diagnosed with high-grade gliomas (HGGs), including DIPG. Detailed genetic sequencing using advanced technology will be performed on tumor tissue from all patients upfront, with return of results within 3 weeks. Patients will then be assigned to one of several unique molecularly-targeted treatment arms based on (and directly targeting) the genetic alterations identified in their tumor. Additionally, all patients with undergo upfront radiation. We will be investigating the effectiveness of molecularly-targeted treatments.

Furthermore, in addition to studying the genetic alterations present in tumor tissue prior to treatment, we will collect blood samples as well as cerebrospinal fluid (CSF) and/or future tumor tissue (if a second surgery is performed) throughout the study. Genomic and immune profiling analyses will be performed on these specimens over time to identify biomarkers (“liquid biopsy” tools) that can predict early response or recurrence to treatment and improve the understanding of why some tumors become resistant to therapy.

TarGeT-SCR is the overarching screening protocol on which all patients must first enroll to confirm eligibility and be assigned to a targeted therapy arm based on their tumor’s unique molecular profile. There are three different options by which patients can screen to allow as much flexibility as possible, including options to submit tissue for genetic sequencing or upload results of previously performed testing.

A high proportion of pediatric HGG and DIPG have alterations in the cell cycle or PI3K/mTOR pathways, which contribute to tumor cell growth, representing potential targets. Our team has recently studied the combination of two oral targeted drugs—ribociclib, a CDK4/6 inhibitor which blocks the cell cycle pathway and everolimus, an mTOR inhibitor which blocks the PI3K/mTOR pathway—which were shown to be safe when administered to children newly diagnosed with HGG and DIPG post-radiotherapy.

In the TarGeT-A arm, we are specifically focusing on children and young adults with DIPG/DMG assigned to treatment with ribociclib and everolimus based on their tumor molecular profile on the phase II trial, through which effectiveness of the combination will be assessed. Patients will receive ribociclib orally days 1-21 and everolimus orally days 1-28 of 28-day cycles.

In addition to studying the genetic alterations present in tumor tissue prior to treatment, we will collect blood samples as well as cerebrospinal fluid (CSF) and/or future tumor tissue (if a second surgery is performed) throughout the study. Genomic and immune profiling analyses will be performed on these specimens over time to identify biomarkers (“liquid biopsy” tools) that can predict early response or recurrence to the combination of ribociclib and everolimus and improve the understanding of why some tumors become resistant to therapy. We will also analyze imaging and patient- and parent-reported quality of life outcomes over time to develop minimally invasive predictors of treatment benefit.

Isocitrate dehydrogenase-1 (IDH1) mutations are found in 6% of pediatric HGG and up to 36% of HGGs in adolescents and young adult with therapeutic and prognostic implications. IDH-mutant gliomas have distinct clinical, pathological, and molecular features including a favorable prognosis and response to therapy compared to their wild-type counterparts. Olutasidenib (FT-2102) is an oral, potent, brain-penetrant selective inhibitor of mutated IDH1 protein. Safety and preliminary efficacy of single-agent olutasidenib in adult patients with relapsed/refractory IDH1-mutant gliomas were recently demonstrated.

In the TarGeT-D arm, children and young adults with IDH1 mutant HGG will be treated with post-radiotherapy combination of olutasidenib and temozolomide. Patients will receive olutasidenib orally days 1-28 and temozolomide orally days 1-5 of 28-day cycles. After 13 cycles with this combination, patients will receive 13 cycles of olutasidenib monotherapy.

In addition to studying the genetic alterations present in tumor tissue prior to treatment, we will collect blood samples as well as cerebrospinal fluid (CSF) and/or future tumor tissue (if a second surgery is performed) throughout the study. Genomic and immune profiling analyses will be performed on these specimens over time to identify biomarkers (“liquid biopsy” tools) that can predict early response or recurrence to the combination of olutasidenib and temozolomide and improve the understanding of why some tumors become resistant to therapy. We will also analyze imaging and patient- and parent-reported quality of life outcomes over time to develop minimally invasive predictors of treatment benefit.