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

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

NCT ID: NCT02015728

Condition: Recurrent Childhood Brain Tumor

Conditions: Official terms:
Brain Neoplasms
Recurrence
Etoposide
Temozolomide
Everolimus
Erlotinib Hydrochloride
Sorafenib
Dasatinib

Conditions: Keywords:
Refractory
Recurrent
Brain
Tumor
Pediatric
Biologically Targeted Therapy
Sorafenib
Everolimus
Erlotinib
Dasatinib
Temozolomide
Etoposide

Study type: Interventional

Study phase: N/A

Overall status: Unknown status

Study design:

Allocation: Non-Randomized

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Device
Intervention name: Tumor biology testing
Description: 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.
Arm group label: Regimen A
Arm group label: Regimen B
Arm group label: Regimen C
Arm group label: Regimen D

Other name: IHC Testing

Other name: Immunohistochemical Screening

Other name: Immunohistochemical Test

Other name: Tumor Markers

Intervention type: Drug
Intervention name: Temozolomide
Description: Temozolomide combined with Etoposide is considered the "best available" combination of low-dose oral cytotoxic agents for patients with refractory or recurrent CNS tumors.
Arm group label: Regimen A
Arm group label: Regimen B
Arm group label: Regimen C
Arm group label: Regimen D

Other name: Temodar

Other name: Temodal

Other name: Temcad

Intervention type: Drug
Intervention name: Etoposide
Description: Etoposide combined with Temozolomide is considered the "best available" combination of low-dose oral cytotoxic agents for patients with refractory or recurrent CNS tumors.
Arm group label: Regimen A
Arm group label: Regimen B
Arm group label: Regimen C
Arm group label: Regimen D

Other name: Etopophos

Other name: Vepesid

Intervention type: Drug
Intervention name: Sorafenib
Description: Sorafenib is a broad-spectrum kinase inhibitor.
Arm group label: Regimen A

Other name: Nexavar

Intervention type: Drug
Intervention name: Everolimus
Description: Everolimus is an mTOR pathway inhibitor.
Arm group label: Regimen B

Other name: Zortress

Other name: Certican

Intervention type: Drug
Intervention name: Erlotinib
Description: Erlotinib is a tyrosine kinase inhibitor of the ERBB family of proteins.
Arm group label: Regimen C

Other name: Tarceva

Intervention type: Drug
Intervention name: Dasatinib
Description: Dasatinib is a broad spectrum SRC inhibitor.
Arm group label: Regimen D

Other name: Sprycel

Summary: 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.

Detailed description: 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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: Patients must have histological confirmation of a brain tumor at diagnosis or relapse for all tumors. There must be documented progression or recurrence of disease by MRI imaging or CSF studies since completion of last tumor-directed medical therapy. Patients may have had surgical resection or radiation of tumor, and need not have measurable or evaluable disease at study entry. Patient's current disease state must be one for which there is no known curative therapy. Age greater than 1 month and less than 30 years at the time of enrollment. BSA greater than 0.3 m2 at the time of enrollment. Karnofsky >/= 50% for patients > 16 years of age, and Lansky >/= 50% for patients 750 - Platelet count > 100,000/uL without platelet transfusion within the past 7 days Adequate renal function defined as creatinine within normal range for age or calculated GFR > 100 ml/min/1.73 m2. Adequate liver function defined as Bilirubin < 1.5 x upper limit of normal and ALT < 2.5 x upper limit of normal. Adequate CNS function: - Patients with known seizure disorder must have seizures adequately controlled with non-enzyme inducing antiepileptic medications - No increase in steroid dose within the past 7 days. Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy: - Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study (6 weeks if prior nitrosourea). - Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor, 14 days for longacting (e.g. PEG-filgrastim) - Biologic (anti-neoplastic agent): At least 7 days or 3 half-lives (whichever is longer) since the completion of therapy with a biologic agent. - Radiation therapy: ≥ 12 weeks must have elapsed from craniospinal radiation; ≥ 2 weeks must have elapsed from focal radiation. - Surgery: > 3 weeks from major surgery. If recent craniotomy, adequate wound healing must be determined by neurosurgical team prior to starting study therapy. - Autologous Stem Cell Transplant or Rescue: No evidence of active graft vs. host disease and ≥ 4 weeks must have elapsed. All patients and/or a legal guardian must sign institutionally approved written informed consent document. Exclusion Criteria: Patients who are breastfeeding, pregnant or refuse to use an effective form of birth control are excluded. Abstinence is considered an effective form of birth control. Patients with uncontrolled infection are excluded. Patients with known bleeding disorders or more than punctate intratumoral hemorrhage are excluded. Patients receiving other anti-neoplastic agents are excluded. Patients on enzyme-inducing anticonvulsive agents are excluded. Patients requiring strong CYP3A4 inducers or inhibitors are excluded. Patients requiring anticoagulation or with uncontrolled bleeding are excluded. Patients on steroids for symptom management must be on a stable dose over the 7 days prior to study enrollment. Patients within 1 year of allogeneic stem cell transplant, patients with active GVHD or requiring immunosuppression are excluded.

Gender: All

Minimum age: 1 Month

Maximum age: 30 Years

Healthy volunteers: No

Locations:

Facility:
Name: Seattle Children's

Address:
City: Seattle
Zip: 98105
Country: United States

Start date: December 2013

Completion date: December 2017

Lead sponsor:
Agency: Seattle Children's Hospital
Agency class: Other

Collaborator:
Agency: Cures Within Reach
Agency class: Other

Source: Seattle Children's Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT02015728