PHASE I STUDIES OF TARCEVATM (ERLOTINIB HYDROCHLORIDE, OSI-774) AS SINGLE AGENT IN CHILDREN WITH REFRACTORY AND RELAPSED MALIGNANT BRAIN TUMORS AND IN COMBINATION WITH IRRADIATION IN NEWLY DIAGNOSED MALIGNANT BRAIN STEM GLIOMA - Tarceva in pediatric brain tumors

• Conditions: refractory and relapsed malignant brain tumors newly diagnosed brain stem glioma; MedDRA version: 9.1Level: PTClassification code 10006131; MedDRA version: 9.1Level: PTClassification code 10018338

• Registration Number: EUCTR2004-005247-10-IT
• Lead Sponsor: FONDAZIONE SENDO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-11-07
• Last Update Posted: 1 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

Written informed consent of patient or parent/guardian. Patients in group 1 must have histologically or cytologically confirmed malignant brain tumor. Disease must be considered refractory to first line or relapsing after conventional therapy or for which no effective conventional treatment exists. Patients in group 2 must have newly diagnosed, histologically proven malignant brain stem glioma, except pilocytic astrocytomas. Age: 1 to &#8804; 21 years of age at study entry Life expectancy: at least 8 weeks No concomitant anti-cancer or investigational drug besides irradiation for group 2. ECOG Performance status <1 or Lansky-Play Scale > 70% and including children with motor paresis due to disease. Hematopoietic function: Absolute neutrophil count > 1.5 x 109/l Platelets > 100 x 109/l Hemoglobin > 8 g/dl Hepatic function: AST/ALT < 2.5 x ULN Bilirubin <1.5 ULN Renal function: Creatinine < 1.5 x ULN for age (1-15 years old: < 65 mmol/l; 15-21 years old: < 110 mmol/l); If serum creatinine is > 1.5 ULN of age, then creatinine clearance (or radioisotope GFR) must be > 70 ml/min/1.73 m2 No other serious concomitant illness No organ toxicity > grade 2 NCI-CTC version 3.0 alopecia and neurological symptoms due to disease Able to comply with study and follow-up procedures Patients must able to take oral medication. Children in group 2 with some difficulties in swallowing may be allowed For all females of child bearing potential a negative pregnancy test must be obtained before registration Patients with reproductive potential must use effective contraception
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients with spontaneous intratumoral hemorrhage will not be included in the study, in exception of small post-biopsy hemorrhage due to biopsy procedure Pregnant and breast feeding woman Uncontrolled intercurrent illness or active infection Chemotherapy within 4 weeks prior to study medication (within 6 weeks, if the regimen contained a nitrosourea) Radiation therapy within 6 weeks prior to study medication Any clinical or non-clinical evidence of pulmonary dysfunction or pre-existing lung disease; Severe cardiac pathology; history of myocardial infarction within the year prior to inclusion Any significant ophthalmologic abnormality, especially severe dry eye syndrome, keratoconjunctivitis sicca, Sjögren syndrome, severe exposure keratitis or any other disorder likely to increase the risk of corneal epithelial lesions Treatment with Coumarin (warfarin)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To establish the Maximum Tolerated Dose (MTD), or the recommended dose for phase II study for single agent and in combination with radiation therapy;Secondary Objective: To define Dose Limiting Toxicities (DLTs) To define the safety profile To characterize pharmacokinetic and pharmacodynamic parameters To evaluate efficacy To evaluate expression and mutations of EGFR with efficacy;Primary end point(s): Safety: Dose Limiting Toxicity (DLT) at 3 weeks for cohort 1, and at 6 weeks for cohort 2 with intermittent evaluation at 3 weeks