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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01234740
First Posted: November 4, 2010
Last Update Posted: March 19, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center
  Purpose

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.


Condition Intervention
Adult Anaplastic Astrocytoma Adult Anaplastic Ependymoma Adult Anaplastic Oligodendroglioma Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Adult Mixed Glioma Recurrent Adult Brain Tumor Tumors Metastatic to Brain Adult Anaplastic Oligoastrocytoma Drug: bafetinib Procedure: microdialysis Other: pharmacological study Other: liquid chromatography Other: mass spectrometry Other: laboratory biomarker analysis Genetic: protein expression analysis Genetic: western blotting Other: immunohistochemistry staining method Procedure: therapeutic conventional surgery

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: BAFETINIB-P1-GBM-01: A Pilot Study Using Intracerebral Microdialysis to Determine the Neuropharmacokinetics of Bafetinib in Patients With Recurrent Brain Tumors

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Area-under-the-concentration-time-curve (AUC) of bafetinib in dialysate [ Time Frame: every hour for 24 hours after first dose of bafetinib ]
  • Peak concentration (Cmax) of bafetinib in dialysate [ Time Frame: every hour for 24 hours after first dose of bafetinib ]
  • AUC of bafetinib in plasma [ Time Frame: 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 ]
  • Cmax of bafetinib in plasma [ Time Frame: 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 Outcome Measures:
  • Determination of adverse events associated with bafetinib in patient with recurrent malignant brain tumors [ Time Frame: 30 days after last dose of bafetinib ]
  • Response rate in patients with malignant brain tumors treated with bafetinib [ Time Frame: 30 days after last dose of bafetinib ]
  • Progression-free survival in patients with malignant brain tumors treated with bafetinib [ Time Frame: 1 year after last dose of bafetinib ]
  • Overall survival in patients with malignant brain tumors treated with bafetinib [ Time Frame: 2 years after last dose of bafetinib ]
  • Assessment for expression of Lyn and Fyn kinases and phosphorylation status in pre-treatment tumor samples. [ Time Frame: Pre-treatment tumor samples ]

Enrollment: 7
Study Start Date: December 2010
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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.
Drug: bafetinib
Given orally
Other Names:
  • dual Bcr-Abl/Lyn tyrosine kinase inhibitor INNO-406
  • INNO-406
  • NS-187
Procedure: microdialysis
Catheter placed intracerebrally during debulking craniotomy or stereotactic biopsy
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: liquid chromatography
Correlative studies
Other Name: LC
Other: mass spectrometry
Correlative studies
Other: laboratory biomarker analysis
Correlative studies
Genetic: protein expression analysis
Correlative studies
Genetic: western blotting
Correlative studies
Other Names:
  • Blotting, Western
  • Western Blot
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry
Procedure: therapeutic conventional surgery
debulking craniotomy

Detailed 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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01234740


Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
South Pasadena Cancer Center
South Pasadena, California, United States, 91030
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Jana Portnow City of Hope Medical Center
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01234740     History of Changes
Other Study ID Numbers: 10134
NCI-2010-01963
First Submitted: September 28, 2010
First Posted: November 4, 2010
Last Update Posted: March 19, 2013
Last Verified: March 2013

Keywords provided by City of Hope Medical Center:
Los Angeles

Additional relevant MeSH terms:
Neoplasms
Glioblastoma
Glioma
Brain Neoplasms
Astrocytoma
Gliosarcoma
Ependymoma
Oligodendroglioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases