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

NCT02015728 | Unknown DMC

• 1 other identifier: SC-9006
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Childhood Brain Tumor

Keywords

Refractory; Recurrent; Brain; Tumor; Pediatric; Biologically Targeted Therapy; Sorafenib; Everolimus; Erlotinib; Dasatinib; Temozolomide; Etoposide

Outcome Measures

Primary Outcomes (1)

• Feasibility

  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.

  3 years

Secondary Outcomes (3)

• Efficacy

  3 years

• Survival

  3 years

• Toxicity

  3 years

Study Arms (4)

Regimen B

EXPERIMENTAL

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.

Device: Tumor biology testing; Drug: Temozolomide; Drug: Etoposide; Drug: Everolimus

Regimen C

EXPERIMENTAL

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.

Device: Tumor biology testing; Drug: Temozolomide; Drug: Etoposide; Drug: Erlotinib

Regimen D

EXPERIMENTAL

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.

Device: Tumor biology testing; Drug: Temozolomide; Drug: Etoposide; Drug: Dasatinib

Regimen A

EXPERIMENTAL

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.

Device: Tumor biology testing; Drug: Temozolomide; Drug: Etoposide; Drug: Sorafenib

Interventions

Tumor biology testing DEVICE

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.

Also known as: IHC Testing, Immunohistochemical Screening, Immunohistochemical Test, Tumor Markers

Regimen A; Regimen B; Regimen C; Regimen D

Temozolomide DRUG

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

Also known as: Temodar, Temodal, Temcad

Regimen A; Regimen B; Regimen C; Regimen D

Etoposide DRUG

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

Also known as: Etopophos, Vepesid

Regimen A; Regimen B; Regimen C; Regimen D

Sorafenib DRUG

Sorafenib is a broad-spectrum kinase inhibitor.

Also known as: Nexavar

Regimen A

Everolimus DRUG

Everolimus is an mTOR pathway inhibitor.

Also known as: Zortress, Certican

Regimen B

Erlotinib DRUG

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

Also known as: Tarceva

Regimen C

Dasatinib DRUG

Dasatinib is a broad spectrum SRC inhibitor.

Also known as: Sprycel

Regimen D

Eligibility Criteria

• Age: 1 Month - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Seattle Children's Hospital: lead
• Cures Within Reach: collaborator

Study Sites (1)

Seattle Children's

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Recurrence; Neoplasms

Interventions

Immunohistochemistry; Temozolomide; Etoposide; etoposide phosphate; Sorafenib; Everolimus; Erlotinib Hydrochloride; Dasatinib

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Sirolimus; Macrolides; Lactones; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiazoles; Sulfur Compounds; Pyrimidines

Study Officials

• Sarah ES Leary, MD

  Seattle Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Study Record Dates

• First Submitted: December 13, 2013
• First Posted: December 19, 2013
• Study Start: December 1, 2013
• Primary Completion: November 1, 2016
• Study Completion: December 1, 2017
• Last Updated: December 15, 2016

Record last verified: 2016-12

Locations

US (1)