Neoplasms

Symptoms and General Pathology

All Conditions

Nervous System Diseases

Rare Diseases

Neoplasm Metastasis

Recurrence

Glioblastoma

Glioma

Brain Neoplasms

Astrocytoma

Ependymoma

Oligodendroglioma

Gliosarcoma

Disease Attributes

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Brain Tumor, Adult

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Oligoastrocytoma

Anaplastic Oligoastrocytoma

Anaplastic Ependymoma

Neuroepithelioma

All Drugs and Chemicals

Amino Acids

Tyrosine Kinase Inhibitors

Bafetinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients undergo intracerebral microdialysis during debulking craniotomy or stereotactic biopsy. Beginning 24 hours later, patients receive oral bafetinib twice daily for 1 day. Beginning at least 2 weeks after surgery, patients continue to receive oral bafetinib twice daily in the absence of disease progression or unacceptable toxicity.

bafetinib

Catheter placed intracerebrally during debulking craniotomy or stereotactic biopsy

microdialysis

pharmacological study

liquid chromatography

mass spectrometry

laboratory biomarker analysis

protein expression analysis

western blotting

immunohistochemistry staining method

therapeutic conventional surgery

Jana Portnow

RATIONALE: Bafetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This clinical trial studies bafetinib in treating patients with recurrent high-grade glioma or brain metastases.

PRIMARY OBJECTIVES:

I. To determine the neuropharmacokinetics (nPK) and systemic levels of bafetinib in patients with recurrent malignant brain tumors.

SECONDARY OBJECTIVES:

I. To investigate the intrapatient variability of nPK parameters as assessed by intracerebral microdialysis.

II. To document the toxicity of bafetinib in this cohort of patients. III. To describe the response rate, progression-free survival, and overall survival in patients with malignant brain tumors treated with bafetinib.

IV. To assess for the expression of Lyn and Fyn kinases and phosphorylation status in pre-treatment tumor samples.

OUTLINE:Patients undergo intracerebral microdialysis during debulking craniotomy or stereotactic biopsy. Beginning 24 hours later, patients receive oral bafetinib twice daily for 1 day. Beginning at least 2 weeks after craniotomy or 1 week after biopsy, patients continue to receive oral bafetinib twice daily in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then every 8 weeks thereafter.

Bafetinib in Treating Patients With Recurrent High-Grade Glioma or Brain Metastases

BAFETINIB-P1-GBM-01: A Pilot Study Using Intracerebral Microdialysis to Determine the Neuropharmacokinetics of Bafetinib in Patients With Recurrent Brain Tumors

National Cancer Institute (NCI)

City of Hope Medical Center

Anti-Infective Agents

Flucytosine

Clotrimazole

Miconazole

Antifungal Agents

Antimetabolites

Patients undergo debulking craniotomy and receive injections of HB1.F3.CD neural stem cells directly into brain tissue on day 0. Patients then receive oral 5-fluorocytosine every 6 hours on days 4-10 in the absence of disease progression or unacceptable toxicity.

flucytosine

polymerase chain reaction

Injected at the time of the surgery to resect the tumor

gene therapy

3-Tesla magnetic resonance imaging

E. coli CD-expressing genetically modified neural stem cells

RATIONALE: Genetically-modified neural stem cells (NSCs) that convert 5-fluorocytosine (5-FC) into the chemotherapy agent 5-FU (fluorouracil) at sites of tumor in the brain may be an effective treatment for glioma.

PURPOSE: This clinical trial studies genetically-modified NSCs and 5-FC in patients undergoing surgery for recurrent high-grade gliomas.

PRIMARY OBJECTIVES:

I. To determine the safety and feasibility of intracerebral administration of NSCs in combination with oral 5-FC in patients with recurrent high-grade gliomas.

SECONDARY OBJECTIVES:

I. To characterize the relationship between intracerebral and systemic concentrations of 5-FC and 5-FU with increasing NSC dose level.

II. To non-invasively assess the presence of 5-FU in the brain with the use of fluorine (19F)-magnetic resonance spectroscopy (MRS)(no longer in effect as of 5/1/2012).

III. To assess for the possible development of immunogenicity against the NSCs.

IV. To assess the intracerebral distribution of NSCs using iron-labeling as a cellular tracker.

V. To gather preliminary imaging data regarding perfusion permeability parameters and imaging characteristics as shown on magnetic resonance imaging (MRI) studies due to the presence of NSCs in the brain.

VI. To determine, at time of autopsy, the fate of the NSCs.

OUTLINE:

This is a dose-escalation study.

After biopsy or surgery to resect tumor, study patients receive injections of genetically modified NSCs directly into brain tissue on day 0. Patients then take oral 5-FC every 6 hours during days 4-10 which is converted to 5-FU in the brain by the NSCs.

Follow-up MRIs of the brain are performed on days 32, 60, and every 2 months thereafter to assess for response and side effects.

A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically-Modified Neural Stem Cells Expressing E.Coli Cytosine Deaminase for Treatment of Recurrent High Grade Gliomas

Measures of feasibility include the incidence of clinically symptomatic intratumoral hemorrhage, CNS infection, seizures, altered mental status, development of focal neurologic deficits, as well as chemotherapy-associated toxicities. All toxicities at each dose level will be summarized using descriptive statistics. Graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Summarized by NSC dose cohort using descriptive statistics and graphs. The Macdonald Criteria will be used to assess response. As of 11/30/2012 patients will no longer undergo these tests.

As of 5/1/2012, study patients will no longer undergo 19F-MRS.

As of 11/30/2012 patients will no longer undergo these tests.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Bafetinib in Treating Patients With Recurrent High-Grade Glioma or Brain Metastases	NCT01234740	Adult Anaplasti... Adult Anaplasti... Adult Anaplasti... Adult Giant Cel... Adult Glioblast... Adult Gliosarco... Adult Mixed Gli... Recurrent Adult... Tumors Metastat... Adult Anaplasti...	bafetinib microdialysis pharmacological... liquid chromato... mass spectromet... laboratory biom... protein express... western blottin... immunohistochem... therapeutic con...	18 Years -	City of Hope Medical Center
Bafetinib in Treating Patients With Recurrent High-Grade Glioma or Brain Metastases	NCT01234740	Adult Anaplasti... Adult Anaplasti... Adult Anaplasti... Adult Giant Cel... Adult Glioblast... Adult Gliosarco... Adult Mixed Gli... Recurrent Adult... Tumors Metastat... Adult Anaplasti...	bafetinib microdialysis pharmacological... liquid chromato... mass spectromet... laboratory biom... protein express... western blottin... immunohistochem... therapeutic con...	18 Years -	City of Hope Medical Center
A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically-Modified Neural Stem Cells Expressing E.Coli Cytosine Deaminase for Treatment of Recurrent High Grade Gliomas	NCT01172964	Adult Anaplasti... Recurrent Grade... Recurrent Grade... Adult Anaplasti... Adult Brain Tum... Adult Giant Cel... Adult Glioblast... Adult Gliosarco... Adult Mixed Gli... Recurrent Adult... Adult Anaplasti... Recurrent High ...	flucytosine polymerase chai... immunohistochem... gene therapy pharmacological... 3-Tesla magneti... laboratory biom... therapeutic con... E. coli CD-expr...	13 Years -	City of Hope Medical Center
A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically-Modified Neural Stem Cells Expressing E.Coli Cytosine Deaminase for Treatment of Recurrent High Grade Gliomas	NCT01172964	Adult Anaplasti... Recurrent Grade... Recurrent Grade... Adult Anaplasti... Adult Brain Tum... Adult Giant Cel... Adult Glioblast... Adult Gliosarco... Adult Mixed Gli... Recurrent Adult... Adult Anaplasti... Recurrent High ...	flucytosine polymerase chai... immunohistochem... gene therapy pharmacological... 3-Tesla magneti... laboratory biom... therapeutic con... E. coli CD-expr...	13 Years -	City of Hope Medical Center

Spots Global Cancer Trial Database for adult anaplastic oligoastrocytoma