Clinical trial NCT02015728: Selecting Patient-Specific Biologically Targeted Therapy for Pediatric Patients With Refractory Or Recurrent Brain Tumors
Official title: The Feasibility of Selecting Patient-Specific Biologically Targeted Therapy With Sorafenib, Everolimus, Erlotinib or Dasatinib for Pediatric Patients With Refractory Or Recurrent Brain Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Recurrent Childhood Brain Tumor
Keywords: Refractory
Recurrent
Brain
Tumor
Pediatric
Biologically Targeted Therapy
Sorafenib
Everolimus
Erlotinib
Dasatinib
Temozolomide
Etoposide
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
Collaborators: name: Cures Within Reach
First posted: 2013-12-19
Enrollment: 20
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 \</= 16 years of age.

* Neurologic deficits in patients with CNS tumors must have been relatively stable for a minimum of 7 days.
* Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.

Adequate bone marrow function including:

* ANC \> 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.

Primary outcomes:
measure: Feasibility
timeFrame: 3 years
Secondary outcomes:
measure: Efficacy
timeFrame: 3 years
measure: Survival
timeFrame: 3 years
measure: Toxicity
timeFrame: 3 years
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Seattle Children's
state: Washington
Study officials:
affiliation: Seattle Children's Hospital
name: Sarah ES Leary, MD
role: PRINCIPAL_INVESTIGATOR
References: