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

Adult Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01234740
• Other study ID #: 10134
• Secondary ID: NCI-2010-01963
• Status: Completed
• Phase: Phase 1
• First received: September 28, 2010
• Last updated: April 12, 2018
• Start date: December 2010
• Est. completion date: March 2013

Study information

• Verified date: April 2018
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have radiographic findings consistent with either:

• Recurrent high-grade glioma, or

• Metastatic disease to the brain that has progressed after treatment with whole brain radiation therapy or stereotactic radiosurgery; patients who have a resectable brain metastasis as the only site of disease (i.e., no evidence of systemic disease), are not eligible to participate

• Patients who are in need of a surgical debulking or a stereotactic biopsy for the purpose of diagnosis or differentiating between tumor progression versus treatment-induced effects following radiation therapy +/- chemotherapy will be eligible to participate in the microdialysis part of the study prior to beginning cycle 1 of bafetinib if the study neurosurgeon thinks there is a likelihood of being able to place the microdialysis catheter into residual tumor (enhancing brain tissue)

• Patients who choose not to participate in the microdialysis part of the study may enroll in the study and start treatment at cycle 1 of bafetinib

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for 3 months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately

• Patients must have a Karnofsky Performance Status (KPS) >= 60%

• If corticosteroids are required for controlling cerebral edema, patients must be on a stable dose for at least 1 week prior to enrollment

• Patients must not be taking any hepatic enzyme-inducing anticonvulsants (phenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine) for at least 2 weeks prior to enrollment

• Absolute neutrophil count >= 1500 cells/mm^3

• Platelet count >= 100,000 cells/mm^3

• Total bilirubin =< 2.0 mg/dl

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 3 times the institutional upper limit of normal

• Alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 3 times the institutional upper limit of normal

• Serum creatinine =< 1.5 x the institutional upper limit of normal

• QTc interval < 480 msec on electrocardiogram (ECG)

• All subjects must have the ability to understand and the willingness to sign a written informed consent

• Patients must have recovered from any toxicity of prior therapies (including brain radiation); an interval of at least 6 weeks must have elapsed since the completion of a nitrosourea-containing chemotherapy regimen; patients who have undergone a recent craniotomy cannot begin bafetinib until at least 2 weeks after the surgery

Exclusion Criteria:

• Patients who are currently receiving chemotherapy or are enrolled in another treatment clinical trial

• Patients with a coagulopathy or bleeding disorder

• Patients on anticoagulant drug therapy or medications that inhibit platelet function, such as ibuprofen or other non-steroidal anti-inflammatory drugs

• Clinically evident congestive heart failure > class II of the New York Heart Association (NYHA) guidelines

• Clinically significant cardiac arrhythmias

• Patients taking a drug that can prolong the QT interval; if a potential study patient is taking one of the prohibited drugs but s/he can safely stop it, then a washout period of >= 7 days is required prior to starting bafetinib

• History or signs of active coronary artery disease with or without angina pectoris

• Patients who have a serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol or may not be able to comply with the safety monitoring requirements of the study

• Human immunodeficiency virus (HIV)-positive patients receiving anti-retroviral therapy are excluded from the study due to the possibility of pharmacokinetic (PK) interactions with bafetinib; however, patients will not be routinely screened for HIV

• Female patients who are pregnant or breast-feeding

• Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals

• Patients who have not recovered from the toxicities of prior chemotherapy or radiotherapy

Related Conditions & MeSH terms

• Adult Anaplastic Astrocytoma
• Adult Anaplastic Ependymoma
• Adult Anaplastic Oligoastrocytoma
• Adult Anaplastic Oligodendroglioma
• Adult Giant Cell Glioblastoma
• Adult Glioblastoma
• Adult Gliosarcoma
• Adult Mixed Glioma
• Astrocytoma
• Brain Neoplasms
• Ependymoma
• Glioblastoma
• Glioma
• Gliosarcoma
• Neoplasms
• Oligodendroglioma
• Recurrent Adult Brain Tumor
• Tumors Metastatic to Brain

Intervention

Drug:
• bafetinib
Given orally

Procedure:
• microdialysis
Catheter placed intracerebrally during debulking craniotomy or stereotactic biopsy

Other:
• pharmacological study
Correlative studies
• liquid chromatography
Correlative studies
• mass spectrometry
Correlative studies
• laboratory biomarker analysis
Correlative studies

Genetic:
• protein expression analysis
Correlative studies
• western blotting
Correlative studies

Other:
• immunohistochemistry staining method
Correlative studies

Procedure:
• therapeutic conventional surgery
debulking craniotomy

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California
United States	South Pasadena Cancer Center	South Pasadena	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area-under-the-concentration-time-curve (AUC) of bafetinib in dialysate		every hour for 24 hours after first dose of bafetinib
Primary	Peak concentration (Cmax) of bafetinib in dialysate		every hour for 24 hours after first dose of bafetinib
Primary	AUC of bafetinib in plasma		1, 2, 3, 4, 6, 8, and 12 hours after the first dose of bafetinib and then 1, 2, 3, 4, 6, 8, and 12 hours after the second dose of bafetinib
Primary	Cmax of bafetinib in plasma		1, 2, 3, 4, 6, 8, and 12 hours after the first dose of bafetinib and then 1, 2, 3, 4, 6, 8, and 12 hours after the second dose of bafetinib
Secondary	Determination of adverse events associated with bafetinib in patient with recurrent malignant brain tumors		30 days after last dose of bafetinib
Secondary	Response rate in patients with malignant brain tumors treated with bafetinib		30 days after last dose of bafetinib
Secondary	Progression-free survival in patients with malignant brain tumors treated with bafetinib		1 year after last dose of bafetinib
Secondary	Overall survival in patients with malignant brain tumors treated with bafetinib		2 years after last dose of bafetinib
Secondary	Assessment for expression of Lyn and Fyn kinases and phosphorylation status in pre-treatment tumor samples.		Pre-treatment tumor samples