The Feasibility of Selecting Patient-Specific Biologically Targeted Therapy With Sorafenib, Everolimus, Erlotinib or Dasatinib for Pediatric Patients With Refractory Or Recurrent Brain Tumors
Overview
- Phase
- Not Applicable
- Intervention
- Tumor biology testing
- Conditions
- Recurrent Childhood Brain Tumor
- Sponsor
- Seattle Children's Hospital
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Feasibility
- Last Updated
- 9 years ago
Overview
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.
Investigators
Sarah Leary
Associate Professor of Pediatrics
Seattle Children's Hospital
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
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.
Arms & Interventions
Regimen B
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.
Intervention: Tumor biology testing
Regimen B
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.
Intervention: Temozolomide
Regimen B
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.
Intervention: Etoposide
Regimen B
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.
Intervention: Everolimus
Regimen C
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.
Intervention: Tumor biology testing
Regimen C
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.
Intervention: Temozolomide
Regimen C
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.
Intervention: Etoposide
Regimen C
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.
Intervention: Erlotinib
Regimen D
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.
Intervention: Tumor biology testing
Regimen D
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.
Intervention: Temozolomide
Regimen D
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.
Intervention: Etoposide
Regimen D
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.
Intervention: Dasatinib
Regimen A
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.
Intervention: Tumor biology testing
Regimen A
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.
Intervention: Temozolomide
Regimen A
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.
Intervention: Etoposide
Regimen A
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.
Intervention: Sorafenib
Outcomes
Primary Outcomes
Feasibility
Time Frame: 3 years
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.
Secondary Outcomes
- Efficacy(3 years)
- Survival(3 years)
- Toxicity(3 years)