AEE788 and Everolimus in Treating Patients With Recurrent or Relapsed Glioblastoma Multiforme

NCT00107237 | Completed Phase 1

• 3 other identifiers: CAEE788A2106UCLA-0409004-01CDR0000422335
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: AEE788 and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving AEE788 together with everolimus may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of AEE788 when given together with everolimus and to see how well they work in treating patients with recurrent or relapsed glioblastoma multiforme.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult glioblastoma; recurrent adult brain tumor; adult giant cell glioblastoma; adult gliosarcoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose and dose-limiting toxicity of AEE788

Secondary Outcomes (5)

• Safety

• Tolerability

• Single-dose and repeated-dose pharmacokinetic profile

• Efficacy (response rate, progression-free survival, and overall survival)

• Antiangiogenic effects

Study Arms (2)

AEE788 200 mg + RAD001 5 mg

EXPERIMENTAL

AEE788 200 mg qd, RAD001 5 mg qd

Drug: AEE788; Drug: everolimus

AEE788 150 mg + RAD001 5mg

EXPERIMENTAL

AEE788 150 mg qd, RAD001 5 mg qod

Drug: AEE788; Drug: everolimus

Interventions

AEE788 DRUG

AEE788 was available in the form of a hard gelatin capsule of 50 mg or 100 mg strengths and packaged in bottles.

AEE788 150 mg + RAD001 5mg; AEE788 200 mg + RAD001 5 mg

everolimus DRUG

Everolimus was formulated as tablets of 2.5 mg and 5 mg strength and supplied in blister packs.

Also known as: RAD001

AEE788 150 mg + RAD001 5mg; AEE788 200 mg + RAD001 5 mg

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed glioblastoma multiforme, meeting 1 of the following criteria: * Phase I * In first or second recurrence or relapse * At least 1 measurable or evaluable enhancing lesion by gadolinium MRI (Gd-MRI) of the brain within the past 3 weeks * Phase II, group 1 * In first or second recurrence or relapse by Gd-MRI of the brain within the past 3 weeks * Requires tumor biopsy OR surgical resection for tumor debulking or for confirmation of recurrence * Phase II, group 2 * In first recurrence or relapse * At least 1 bidimensionally measurable enhancing lesion (≥ 1.5 cm\^2 using product of the largest perpendicular diameters) by Gd-MRI of the brain within the past 3 weeks * Multifocal disease allowed PATIENT CHARACTERISTICS: Performance status * Karnofsky 70-100% Life expectancy * At least 12 weeks Hematopoietic * Absolute neutrophil count ≥ 1,500/mm\^3 * Hemoglobin ≥ 9 g/dL * Platelet count ≥ 100,000/mm\^3 Hepatic * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST and ALT ≤ 2.5 times ULN * No acute or chronic liver disease Renal * Total calcium (corrected) normal\* * Creatinine ≤ 1.5 times ULN OR * Creatinine clearance ≥ 50 mL/min * No proteinuria by dipstick OR * Total urinary protein ≤ 500 mg AND creatinine clearance ≥ 50 mL/min by 24-hour urine collection * No acute or chronic renal disease NOTE: \*Supplements allowed Cardiovascular * LVEF ≥ 45% by MUGA or echocardiogram * No complete left bundle branch block * No requirement for a cardiac pacemaker * No congenital long QT syndrome * No ventricular or atrial tachyarrhythmias * No clinically significant resting bradycardia, defined as \< 50 beats per minute * QTc ≤ 480 msec by ECG * No right bundle branch block and left anterior hemiblock (bifascicular block) * No uncontrolled hypertension OR history of labile hypertension * No unstable angina pectoris OR angina pectoris occurrence within the past 3 months * No congestive heart failure * No acute myocardial infarction within the past 3 months * No history of poor compliance with an antihypertensive regimen * No other impaired cardiac function or clinically significant cardiac disease Gastrointestinal * No unresolved diarrhea ≥ grade 2 * No impairment of gastrointestinal (GI) function or GI disease that would significantly alter absorption of study drugs, including any of the following: * Ulcerative disease * Uncontrolled nausea * Vomiting * Malabsorption syndrome Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception * Potassium normal\* * Magnesium normal\* * Phosphorus normal\* * Cholesterol ≤ 300 mg/dL (treatment allowed) * Triglycerides ≤ 2.5 times ULN (treatment allowed) * No known HIV positivity * No peripheral neuropathy ≥ grade 2 * No uncontrolled diabetes * No active or uncontrolled infection * No other severe and/or uncontrolled medical condition that would preclude study participation or compliance * No contraindication to MRI, including any of the following: * Cardiac pacemaker * Ferromagnetic metal implants other than those approved as safe for use with magnetic resonance scanners (e.g., some types of aneurysm clips or shrapnel) * Claustrophobia * Obesity exceeding magnetic resonance equipment limits * No other clinically significant primary malignancy requiring active intervention NOTE: \*Supplements allowed PRIOR CONCURRENT THERAPY: Biologic therapy * More than 2 weeks since prior hematopoietic colony-stimulating factors (e.g., filgrastim \[G-CSF\] or sargramostim \[GM-CSF\]) except epoetin alfa * More than 2 weeks since prior immunotherapy and recovered * No concurrent biologic therapy * No concurrent prophylactic hematopoietic growth factors (e.g., G-CSF or GM-CSF) unless approved by the study sponsor Chemotherapy * More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered * Prior polifeprosan 20 with carmustine implant (Gliadel® wafer) allowed * No other concurrent chemotherapy Endocrine therapy * Must be on stable or deceasing doses of steroids for at least 7 days before baseline Gd-MRI of the brain and before starting study drug * No concurrent tamoxifen Radiotherapy * More than 4 weeks since prior radiotherapy and recovered * No concurrent radiotherapy Surgery * More than 1 week since prior tumor biopsy * More than 2 weeks since prior surgical resection * More than 2 weeks since prior major non-CNS surgery and recovered * No prior small bowel resection Other * At least 2 weeks since prior and no concurrent enzyme-inducing anticonvulsant drugs * More than 4 weeks since prior investigational drugs and recovered * No prior epidermal growth factor receptor- or ErbB-2-directed therapy (phase II only) * No prior vascular endothelial growth factor (VEGF) or VEGF receptor-directed therapy (phase II only) * No prior mTOR-directed therapy (phase II only) * No concurrent therapeutic warfarin * No concurrent treatment with any medication that may prolong QT interval, including any of the following: * Quinidine * Procainamide * Disopyramide * Amiodarone * Sotalol * Bretylium * Ibutilide * Thioridazine * Mesoridazine * Chlorpromazine * Amitriptyline * Imipramine * Desipramine * Doxepin * Erythromycin * Clarithromycin * Ketoconazole * Halofantrine * Quinine * Chloroquine * Mefloquine * Moxifloxacin * Gatifloxacin * Pimozide * Risperidone * Ziprasidone * Venlafaxine * Maprotiline * Lithium * Pentamidine * Droperidol * Dolasetron * No concurrent digoxin or verapamil * No concurrent tacrolimus * No other concurrent investigational agents

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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095-1781, United States

Location

Duke Univaersity Medical Center

Durham, North Carolina, 27710, United States

Location

MD Anderson Cancer Center/University of Texas

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Brain Neoplasms; Gliosarcoma

Interventions

AEE 788; Everolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: April 5, 2005
• First Posted: April 6, 2005
• Study Start: October 1, 2003
• Primary Completion: June 1, 2006
• Study Completion: June 1, 2006
• Last Updated: June 12, 2013

Record last verified: 2013-06

Locations

US (3)