Safety Study of Tarceva in Children With Refractory and Relapsed Malignant Brain Tumors and Newly Diagnosed Brain Stem Glioma

This study has been completed.
Sponsor:
Information provided by:
Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier:
NCT00418327
First received: January 3, 2007
Last updated: August 6, 2009
Last verified: August 2009
  Purpose

The purpose of this study is to establish the recommended dose/Maximum Tolerated Dose (MTD) of Tarceva in children as single agent and in combination with radiation therapy


Condition Intervention Phase
Malignant Brain Tumor
Brain Stem Glioma,
Drug: Tarceva (Erlotinib Hydrochloride)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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 Brain Stem Glioma

Resource links provided by NLM:


Further study details as provided by Gustave Roussy, Cancer Campus, Grand Paris:

Primary Outcome Measures:
  • To establish the recommended dose / Maximum Tolerated Dose (MTD) the for phase II study for single agent and in combination with radiation therapy [ Time Frame: End of recruitment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To define Dose Limiting Toxicities (DLTs) [ Time Frame: 3 cycles-6 cycles ] [ Designated as safety issue: Yes ]
  • To define the safety profile [ Time Frame: End of treatment ] [ Designated as safety issue: Yes ]
  • To characterize the pharmacokinetic behavior of TarcevaTM in children with brain tumors as a single agent and in combination with radiation therapy [ Time Frame: Cycles 1,2,3,4,5,6 ] [ Designated as safety issue: Yes ]
  • To evaluate efficacy [ Time Frame: Cycles 2,4,6, end of treatment ] [ Designated as safety issue: No ]
  • To evaluate expression and mutations of EGFR with efficacy [ Time Frame: End of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: June 2005
Intervention Details:
    Drug: Tarceva (Erlotinib Hydrochloride)
    tablets of 25 mg, 100 mg and 150 mg 75 to 150 mg/m² Once daily
Detailed Description:

Prognosis in relapsing malignant brain tumors is poor. Those in brain stem gliomas is dismal; median survival of these children does not exceed 9 months. Radiation therapy may result in early and transient amelioration of symptoms, but have not contributed to increase or prolong survival. Moreover, chemotherapy has not increased this outcome to date.Prados et al. reported encouraging results from a phase I study of TarcevaTM/OSI-774 alone or with temozolomide (TMZ) in patients with malignant gliomas. Of 25 evaluated patients, 6 experienced PR: 4 GBM (glioblastoma multiforme) and 1 grade 3 astrocytoma treated with TarcevaTM alone, 1 GBM treated with TarcevaTM/TMZ; 2 had minor responses, and 3 stable diseases. These results in malignant glioma and the lack of efficacy in brain stem glioma with current treatment suggests the evaluation of this new therapeutic agent in children with relapsed brain tumors and upfront at diagnosis in brain stem glioma in combination with radiation therapy.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed malignant brain tumor
  • Disease must be considered refractory to first line or relapsing after conventional therapy and for which no effective conventional treatment exists.·
  • Newly diagnosed, histologically proven brain stem glioma, except pilocytic astrocytomas.
  • Age: 1 to ≤ 21 years of age at study entry
  • Life expectancy: at least 8 weeks
  • ECOG Performance status ≤ 1 or Lansky-Play Scale>= 70%, and including children with motor paresis due to disease
  • Measurable or evaluable disease
  • No other serious concomitant illness
  • No organ toxicity > grade 2 NCI-CTC AE v3.0, except alopecia and neurological symptoms due to disease

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)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00418327

Locations
France
Institut Gustave Roussy
Villejuif, France, 94805
Sponsors and Collaborators
Gustave Roussy, Cancer Campus, Grand Paris
Investigators
Study Chair: Vassal Gilles, Pr. Gustave Roussy, Cancer Campus, Grand Paris
  More Information

No publications provided by Gustave Roussy, Cancer Campus, Grand Paris

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Geoerger Birgit/Coordinating Physician, Institut Gustave Roussy
ClinicalTrials.gov Identifier: NCT00418327     History of Changes
Other Study ID Numbers: CSET 1120
Study First Received: January 3, 2007
Last Updated: August 6, 2009
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Gustave Roussy, Cancer Campus, Grand Paris:
Tarceva
refractory and relapsed malignant brain tumors
newly diagnosed brain stem glioma

Additional relevant MeSH terms:
Brain Neoplasms
Glioma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014