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Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Brain Tumor, Childhood

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Anti-Infective Agents

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Temozolomide

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Sorafenib

Erlotinib Hydrochloride

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Antineoplastic Agents, Alkylating

Alkylating Agents

Sirolimus

Temsirolimus

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Protein Kinase Inhibitors

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Immunologic Factors

Tyrosine

Depending on tumor biology testing, subjects assigned to Regimen B will receive:

Temozolomide 150 mg/m2/dose daily PO on days 1-5, Etoposide 50 mg/m2/dose daily PO on days 1-12, and Everolimus 3 mg/m2/dose daily PO on days 1-28. Cycles will be repeated every 28 days for up to 12 cycles.

Depending on tumor biology testing, subjects assigned to Regimen C will receive:

Temozolomide 150 mg/m2/dose daily PO on days 1-5, Etoposide 50 mg/m2/dose daily PO on days 1-12, and Erlotinib 85 mg/m2/dose daily PO on days 1-28. Cycles will be repeated every 28 days for up to 12 cycles.

Depending on tumor biology testing, subjects assigned to Regimen D will receive:

Temozolomide 150 mg/m2/dose daily PO on days 1-5, Etoposide 50 mg/m2/dose daily PO on days 1-12, and Dasatinib 60 mg/m2/dose BID PO on days 1-28. Cycles will be repeated every 28 days for up to 12 cycles.

Depending on tumor biology testing, subjects assigned to Regimen A will receive:

Temozolomide 150 mg/m2/dose daily PO on days 1-5, Etoposide 50 mg/m2/dose daily PO on days 1-12, and Sorafenib 150 mg/m2/dose BID PO on days 1-28. Cycles will be repeated every 28 days for up to 12 cycles.

Tumor biology studies will be performed in a CLIA-approved clinical pathology laboratory using standard procedures. Immunohistochemical (IHC) testing will be performed on formalin fixed tumor obtained at the time of diagnosis and/or relapse. Results will be interpreted by a qualified pediatric pathologist and will be scored on a scale of 0 to 4+ commenting on both percentage of positive cells and intensity of staining. Results will further be reported as a binary result (positive/negative). If more than one tumor specimen is available from different surgical procedures (e.g. initial diagnosis and relapse), the results from the relapse specimen will be prioritized. Results will determine kinase inhibitor treatment arm assignment which will be administered in addition to the "best available" combination of low-dose oral cytotoxic agents, including temozolomide and etoposide.

Tumor biology testing

Temozolomide combined with Etoposide is considered the "best available" combination of low-dose oral cytotoxic agents for patients with refractory or recurrent CNS tumors.

Etoposide combined with Temozolomide is considered the "best available" combination of low-dose oral cytotoxic agents for patients with refractory or recurrent CNS tumors.

Sorafenib is a broad-spectrum kinase inhibitor.

Erlotinib is a tyrosine kinase inhibitor of the ERBB family of proteins.

Erlotinib

Dasatinib is a broad spectrum SRC inhibitor.

Sarah ES Leary, MD

This research study is a Feasibility clinical trial. In this trial, researchers are trying to figure out whether a medication can be chosen based on rapid testing done on tumor tissue. Information from a feasibility or pilot trial will hopefully help researchers plan larger trials in the future to determine the effect of this therapy.

This research study will assign a specific drug treatment based on lab tests performed on the participant's tumor from tumor tissue taken from a biopsy done when he/she was first diagnosed or if taken when he/she relapsed or progressed. All participants will get Temozolomide and Etoposide to start. Then depending on review of the participant's tumor tissue he/she will also receive one of the following: Sorafenib, Everolimus, Erlotinib, or Dasatinib.

The purpose of this research study is to learn about the feasibility of obtaining and using information from studies done on tumor tissue in order to help make treatment decisions for patients with relapsed or refractory pediatric brain tumors. The investigators also want to find out the effects this therapy has on the participant and the participant's brain tumor.

Selecting Patient-Specific Biologically Targeted Therapy for Pediatric Patients With Refractory Or Recurrent Brain Tumors

The Feasibility of Selecting Patient-Specific Biologically Targeted Therapy With Sorafenib, Everolimus, Erlotinib or Dasatinib for Pediatric Patients With Refractory Or Recurrent Brain Tumors

It will be considered feasible to obtain individual biologic testing if at least 80% of patients receive results of biology studies within two weeks of study enrollment.

It will be considered feasible to treat patients based on biologic testing if at least and 50% of patients who consent for biology testing start therapy with one of four regimens within four weeks of study enrollment.

Efficacy endpoint for patients with evaluable or measurable disease will be best objective response (CR, PR, SD or PD) measured by MRI imaging.

Survival endpoints will be estimated including time to progression as well as progression-free and overall survival rates at the 6 month, 1 year and 2 year time point from start of study treatment.

Toxicity endpoints will be descriptive and include grading of patient toxicity according to the National Cancer Institute common terminology criteria for adverse events (CTCAE version 4.0). This study is not intended or powered to compare toxicity between treatment arms. The tolerability of selected therapy with the addition of a kinase inhibitor will be described for all patients as a group.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Selecting Patient-Specific Biologically Targeted Therapy for Pediatric Patients With Refractory Or Recurrent Brain Tumors	NCT02015728	Recurrent Child...	Tumor biology t... Temozolomide Etoposide Sorafenib Everolimus Erlotinib Dasatinib	1 Month - 30 Years	Seattle Children's Hospital
Selecting Patient-Specific Biologically Targeted Therapy for Pediatric Patients With Refractory Or Recurrent Brain Tumors	NCT02015728	Recurrent Child...	Tumor biology t... Temozolomide Etoposide Sorafenib Everolimus Erlotinib Dasatinib	1 Month - 30 Years	Seattle Children's Hospital

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