Imatinib Mesylate, Vatalanib, and Hydroxyurea in Treating Patients With Recurrent or Relapsed Malignant Glioma

NCT00387933 | Completed Phase 1

• 3 other identifiers: Pro00006014DUMC-7019-06-3R1NOVARTIS-DUMC-7019-06-3R1
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

recurrent adult brain tumor; adult glioblastoma; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; adult gliosarcoma; adult giant cell glioblastoma; adult anaplastic ependymoma; adult brain stem glioma; adult mixed glioma; adult pineal gland astrocytoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose and dose-limiting toxicity of imatinib mesylate and vatalanib when administered with hydroxyurea

  1 Year

Secondary Outcomes (4)

• Safety

  1.5 Years

• Tolerability

  1 Year

• Pharmacokinetic

  1.5 Years

• Antiangiogenic effects

  1 Year

Study Arms (1)

Gleevec + PTK787/ZK 22584 + Hydroxyurea

EXPERIMENTAL

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.

Drug: hydroxyurea; Drug: imatinib mesylate; Drug: vatalanib

Interventions

hydroxyurea DRUG

Also known as: HU, hydrea

Gleevec + PTK787/ZK 22584 + Hydroxyurea

imatinib mesylate DRUG

Also known as: Gleevec

Gleevec + PTK787/ZK 22584 + Hydroxyurea

vatalanib DRUG

Also known as: PTK787

Gleevec + PTK787/ZK 22584 + Hydroxyurea

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Duke University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Reardon DA, Egorin MJ, Desjardins A, Vredenburgh JJ, Beumer JH, Lagattuta TF, Gururangan S, Herndon JE 2nd, Salvado AJ, Friedman HS. Phase I pharmacokinetic study of the vascular endothelial growth factor receptor tyrosine kinase inhibitor vatalanib (PTK787) plus imatinib and hydroxyurea for malignant glioma. Cancer. 2009 May 15;115(10):2188-98. doi: 10.1002/cncr.24213.

  PMID: 19248046 RESULT

MeSH Terms

Conditions

Central Nervous System Neoplasms; Brain Neoplasms; Glioblastoma; Astrocytoma; Oligodendroglioma; Gliosarcoma; Ependymoma; Glioma

Interventions

Hydroxyurea; Imatinib Mesylate; vatalanib

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Brain Diseases; Central Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals; Benzamides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• David A. Reardon, MD

  Duke Cancer Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2006
• First Posted: October 13, 2006
• Study Start: July 1, 2005
• Primary Completion: January 1, 2009
• Last Updated: October 14, 2015

Record last verified: 2012-11

Locations

US (1)