- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00387933
Imatinib Mesylate, Vatalanib, and Hydroxyurea in Treating Patients With Recurrent or Relapsed Malignant Glioma
Phase I Dose Escalation of Gleevec in Combination With PTK787/ZK 222584 (PTK/ZK) Plus Hydroxyurea
RATIONALE: Imatinib mesylate, vatalanib, and hydroxyurea may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vatalanib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving imatinib mesylate and vatalanib together with hydroxyurea may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of imatinib mesylate and vatalanib when given together with hydroxyurea in treating patients with recurrent or relapsed malignant glioma.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
OBJECTIVES:
- Determine the maximum tolerated dose and dose-limiting toxicity of imatinib mesylate and vatalanib when administered with hydroxyurea in patients with recurrent or relapsed grade 3 or 4 malignant glioma.
- Determine the safety and tolerability of this regimen in these patients.
- Determine the single-dose and repeated-dose pharmacokinetic profiles of imatinib mesylate (in serum) and vatalanib in these patients.
- Determine the pre- and post-treatment antiangiogenic effects of this regimen in these patients, using dynamic contrast-enhanced MRI to evaluate changes in the extent of vascular permeability, perfusion, and relative tumor blood volume.
- Determine whether changes in diffusion-weighted images MRI (quantitated by apparent diffusion coefficient maps) correlate with tumor cellularity and tumor cell death in patients treated with this regimen.
- Determine antitumor activity of this regimen, in terms of radiographic response, progression-free survival, and overall survival, in these patients.
OUTLINE: This is an open-label, dose-escalation study of imatinib mesylate and vatalanib.
Patients receive oral vatalanib once daily, oral imatinib mesylate once daily, and oral hydroxyurea twice daily on days 1-28*. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients receive vatalanib alone daily on days 1-7 followed by vatalanib, imatinib mesylate, and hydroxyurea on days 8-35 in course 1 only.
Cohorts of 3-6 patients receive escalating doses of imatinib mesylate and vatalanib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
After completion of study treatment, patients will be evaluated for 28 days.
PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
North Carolina
-
Durham, North Carolina, United States, 27710
- Duke Comprehensive Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
Histologically confirmed malignant glioma
- Grade 3 or 4 disease
- In first, second, or third recurrence or relapse
- Multifocal disease allowed
PATIENT CHARACTERISTICS:
- Karnofsky performance status 70-100%
- Life expectancy ≥ 12 weeks
- Absolute neutrophil count > 1,500/mm^3
- Hemoglobin > 9 g/dL
- Platelet count > 100,000/mm^3
- Potassium normal*
- Total calcium (corrected) normal*
- Magnesium normal*
- Phosphorus normal*
- aspartate transaminase (AST) and alanine transaminase (ALT) < 2.5 times upper limit of normal (ULN)
- Bilirubin < 1.5 times ULN
- Negative proteinuria by dipstick OR total urinary protein ≤ 500 mg with creatinine clearance ≥ 50 mL/min by 24-hour urine collection
- Creatinine < 1.5 times ULN OR creatinine clearance > 50 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No acute or chronic liver or renal disease
- left ventricular ejection fraction (LVEF) ≥ 45% by Multi Gated Acquisition Scan (MUGA) or echocardiogram
- No complete left bundle branch block
- No obligate use of a cardiac pacemaker
- No congenital long QT syndrome
- No history of or current ventricular or atrial tachyarrhythmias
- No clinically significant resting bradycardia (i.e., heart rate < 50 beats/minute)
- No right bundle branch block with left anterior hemiblock (bifascicular block)
- No uncontrolled hypertension ≥ grade 2, history of labile hypertension, or history of poor compliance with an antihypertensive regimen
- No concurrent unstable angina pectoris or angina pectoris within the past 3 months
- No congestive heart failure (CHF)
- No history of CHF or arrhythmias requiring concurrent digoxin or verapamil
- No acute myocardial infarction within the past 3 months
- No other impaired cardiac function or clinically significant cardiac disease
- No peripheral neuropathy ≥ grade 2
- No unresolved diarrhea ≥ grade 2
- No uncontrolled diabetes
- No active or uncontrolled infection requiring intravenous antibiotics
No impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of vatalanib, hydroxyurea, and/or everolimus, including any of the following:
- Ulcerative disease
- Uncontrolled nausea, vomiting, or diarrhea
- Malabsorption syndrome
- Small bowel resection
- No other concurrent severe and/or uncontrolled medical condition that would preclude study participation or compliance
- No known HIV positivity
- No other primary malignancy that is clinically significant or requires active intervention NOTE: *Supplement allowed
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- More than 2 weeks since prior tumor biopsy (4 weeks since prior surgical resection)
- Prior polifeprosan 20 with carmustine implant (Gliadel® wafer) allowed at discretion of principal investigator
- Prior hydroxyurea allowed
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and 1 week for metronomic-dosed chemotherapy [e.g., daily etoposide hydrochloride or cyclophosphamide]) and recovered
- More than 4 weeks since prior radiotherapy and recovered
- More than 2 weeks since prior immunotherapy and recovered
- More than 4 weeks since prior investigational drugs and recovered
- No prior platelet-derived growth factor- or vascular endothelial growth factor-directed therapies
More than 2 weeks since prior hematopoietic colony-stimulating factor (e.g., filgrastim [G-CSF] or sargramostim [Granulocyte-macrophage colony-stimulating factor (GM-CSF)])
- Prior epoetin alfa allowed
- No concurrent warfarin
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Gleevec + PTK787/ZK 22584 + Hydroxyurea
Patients with recurrent or relapsing glioblastoma multiforme (GBM) will be given daily doses of Gleevec and PTK787/ZK 22584 orally in combination with fixed doses of hydroxyurea.
|
Other Names:
Other Names:
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Maximum tolerated dose and dose-limiting toxicity of imatinib mesylate and vatalanib when administered with hydroxyurea
Time Frame: 1 Year
|
1 Year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety
Time Frame: 1.5 Years
|
1.5 Years
|
|
Tolerability
Time Frame: 1 Year
|
1 Year
|
|
Pharmacokinetic
Time Frame: 1.5 Years
|
To characterize the single-dose and repeated-dose pharmacokinetic (PK) profiles of imatinib mesylate (in serum) and PTK787/ZK 22584 combination therapy in this patient population.
|
1.5 Years
|
Antiangiogenic effects
Time Frame: 1 Year
|
pre- and post-treatment, of imatinib mesylate, PTK787/ZK 22584 and hydroxyurea combination therapy, using Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) to evaluate changes in the extent of vascular permeability, perfusion and relative tumor blood volume; to explore assessment of tumor cellularity and tumor cell death by changes in diffusion weighted imaging magnetic resonance imaging (DWI-MRI) as quantitated by apparent diffusion coefficient maps (ADC maps). To note the anti-tumor activity of this regimen in terms of radiographic response, progression-free survival and overall survival. |
1 Year
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Nervous System Diseases
- Neoplasms
- Neoplasms by Site
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Antisickling Agents
- Imatinib Mesylate
- Hydroxyurea
- Vatalanib
Other Study ID Numbers
- Pro00006014
- DUMC-7019-06-3R1
- NOVARTIS-DUMC-7019-06-3R1
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Brain and Central Nervous System Tumors
-
Children's Hospital Los AngelesUnknownBrain and Central Nervous System TumorsUnited States, Canada, Australia, Switzerland, New Zealand
-
Emory UniversityNational Cancer Institute (NCI)CompletedBrain and Central Nervous System TumorsUnited States
-
Abramson Cancer Center of the University of PennsylvaniaNational Cancer Institute (NCI)CompletedBrain and Central Nervous System TumorsUnited States
-
Duke UniversityNational Cancer Institute (NCI)CompletedBrain and Central Nervous System TumorsUnited States
-
Duke UniversityNational Cancer Institute (NCI)CompletedBrain and Central Nervous System TumorsUnited States
-
Pediatric Brain Tumor ConsortiumNational Cancer Institute (NCI)CompletedVNP40101M in Treating Young Patients With Recurrent, Progressive, or Refractory Primary Brain TumorsBrain and Central Nervous System TumorsUnited States
-
St. Jude Children's Research HospitalCompletedBrain Tumors | Central Nervous System TumorsUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedBrain Tumors | Central Nervous System TumorsUnited States, Australia, Canada
-
University of Colorado, DenverNational Cancer Institute (NCI)CompletedBrain and Central Nervous System TumorsUnited States
-
National Cancer Institute (NCI)CompletedBrain and Central Nervous System Tumors
Clinical Trials on vatalanib
-
Cambridge University Hospitals NHS Foundation TrustCompletedMelanoma (Skin)United Kingdom
-
Northwestern UniversityNovartisCompletedSarcoma | Brain and Central Nervous System TumorsUnited States
-
Louisiana State University Health Sciences Center...NovartisCompletedMetastatic Neuroendocrine TumorsUnited States
-
NovartisBayerCompletedNeoplasm Metastasis | TumorsUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedMyelodysplastic Syndromes | Leukemia | Myelodysplastic/Myeloproliferative NeoplasmsUnited States
-
University of HelsinkiBayerCompleted
-
European Organisation for Research and Treatment...CompletedBrain and Central Nervous System TumorsSwitzerland, Italy, Belgium, Germany, Netherlands
-
M.D. Anderson Cancer CenterNovartisCompletedAcute Myelogenous Leukemia | Chronic Myelogenous Leukemia | Agnogenic Myeloid MetaplasiaUnited States
-
Daniel George, MDNovartisCompletedKidney Cancer | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
University of Michigan Rogel Cancer CenterNovartisCompleted