Erlotinib Alone or in Combination With Radiation Therapy in Treating Young Patients With Refractory or Relapsed Malignant Brain Tumors or Newly Diagnosed Brain Stem Glioma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2007 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00360854
First received: August 3, 2006
Last updated: September 19, 2013
Last verified: June 2007
  Purpose

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving erlotinib together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of erlotinib when given alone or together with radiation therapy in treating young patients with refractory or relapsed malignant brain tumors or newly diagnosed brain stem glioma.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: erlotinib hydrochloride
Genetic: mutation analysis
Genetic: polymorphism analysis
Other: laboratory biomarker analysis
Other: pharmacological study
Radiation: radiation therapy
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Studies of TARCEVA™ (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 National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose of erlotinib hydrochloride when given alone and in combination with radiotherapy [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Dose-limiting toxicities [ Designated as safety issue: Yes ]
  • Safety [ Designated as safety issue: Yes ]
  • Pharmacokinetic behavior of erlotinib hydrocloride [ Designated as safety issue: No ]
  • Efficacy [ Designated as safety issue: No ]
  • Correlation of expression and mutations of epidermal growth factor receptor with treatment response [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: May 2005
Detailed Description:

OBJECTIVES:

Primary

  • Establish the maximum tolerated dose of single-agent erlotinib hydrochloride in pediatric patients with refractory or relapsed malignant brain tumors and in combination with radiotherapy in pediatric patients with newly diagnosed brain stem glioma.

Secondary

  • Determine dose-limiting toxicities of these regimens.
  • Define the safety profile of these regimens.
  • Characterize the pharmacokinetic behavior of erlotinib hydrochloride in these patients.
  • Evaluate the efficacy of these regimens.
  • Correlate expression and mutations of epidermal growth factor receptor with treatment response.

OUTLINE: This is a multicenter, nonrandomized, open-label, dose-escalation study of erlotinib hydrochloride. Patients are assigned to 1 of 2 treatment groups according to disease.

  • Group 1 (refractory or relapsed malignant brain tumors): Patients receive oral erlotinib hydrochloride once daily on days 1-21. Treatment repeats every 21 days in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride 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 (DLT).

  • Group 2 (newly diagnosed brain stem glioma): Patients receive oral erlotinib hydrochloride once daily on days 1-21. Treatment repeats every 21 days in the absence of unacceptable toxicity or disease progression. Beginning on day 1, patients also undergo radiotherapy 5 days a week for 6 weeks .

Cohorts of 1-2 patients receive escalating doses of erlotinib hydrochloride until the MTD is determined. The MTD is defined as the dose resulting in 25% of patients experiencing DLT at 6 weeks.

Blood is collected for pharmacokinetic assessments and pharmacogenetic genotyping for analysis of enzyme polymorphisms. Tumor tissue may be assessed for epidermal growth factor receptor mutations.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following:

    • Histologically or cytologically confirmed malignant brain tumor

      • Refractory to first-line therapy or relapsed after conventional therapy
      • No effective conventional therapy exists
    • Histologically confirmed brain stem glioma

      • Newly diagnosed disease
      • No pilocytic glioma
  • Measurable or evaluable disease

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2 OR Lansky play scale 50-100%

    • Patients with motor paresis due to disease are eligible
    • Neurological deficits must be stable for ≥ 1 week
  • Life expectancy ≥ 8 weeks
  • Absolute neutrophil count > 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 8 g/dL
  • AST/ALT ≤ 2.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • Creatinine < 1.5 times ULN OR creatinine clearance ≥ 70 mL/min
  • No other serious, uncontrolled illness
  • No active infection
  • No organ toxicity ≥ grade 2 except alopecia and neurological symptoms due to disease
  • Must be able to take oral medication

    • Patients with newly diagnosed brain stem glioma with difficulty swallowing may be eligible
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No evidence of pulmonary dysfunction or pre-existing lung disease
  • No myocardial infarction within the past year
  • No severe cardiac pathology
  • No significant ophthalmologic abnormality including, but not limited to, any of the following:

    • Severe dry eye syndrome
    • Keratoconjunctivitis sicca
    • Sjögren's syndrome
    • Severe exposure keratitis
    • Any other disorder likely to increase the risk of corneal epithelial lesions

PRIOR CONCURRENT THERAPY:

  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
  • More than 6 weeks since prior radiotherapy
  • No concurrent warfarin
  • No other concurrent anticancer or investigational agents
  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: NCT00360854

Locations
Ireland
Our Lady's Hospital for Sick Children Crumlin
Dublin, Ireland, 12
United Kingdom
Birmingham Children's Hospital
Birmingham, England, United Kingdom, B4 6NH
Institute of Child Health at University of Bristol
Bristol, England, United Kingdom, BS2 8AE
Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
Cambridge, England, United Kingdom, CB2 2QQ
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
Leicester Royal Infirmary
Leicester, England, United Kingdom, LE1 5WW
Royal Liverpool Children's Hospital, Alder Hey
Liverpool, England, United Kingdom, L12 2AP
Great Ormond Street Hospital for Children NHS Trust
London, England, United Kingdom, WC1N 3JH
Middlesex Hospital
London, England, United Kingdom, W1T 3AA
Central Manchester and Manchester Children's University Hospitals NHS Trust
Manchester, England, United Kingdom, M27 4HA
Sir James Spence Institute of Child Health
Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
Queen's Medical Centre
Nottingham, England, United Kingdom, NG7 2UH
Oxford Radcliffe Hospital
Oxford, England, United Kingdom, 0X3 9DU
Children's Hospital - Sheffield
Sheffield, England, United Kingdom, S10 2TH
Southampton University Hospital NHS Trust
Southampton, England, United Kingdom, SO16 6YD
Royal Marsden NHS Foundation Trust - Surrey
Sutton, England, United Kingdom, SM2 5PT
Royal Belfast Hospital for Sick Children
Belfast, Northern Ireland, United Kingdom, BT12 6BE
Royal Aberdeen Children's Hospital
Aberdeen, Scotland, United Kingdom, AB25 2ZG
Royal Hospital for Sick Children
Edinburgh, Scotland, United Kingdom, EH9 1LF
Royal Hospital for Sick Children
Glasgow, Scotland, United Kingdom, G3 8SJ
Childrens Hospital for Wales
Cardiff, Wales, United Kingdom, CF14 4XW
Sponsors and Collaborators
Children's Cancer and Leukaemia Group
Investigators
Investigator: Darren Hargrave, MD Royal Marsden NHS Foundation Trust
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00360854     History of Changes
Other Study ID Numbers: CDR0000481539, CCLG-NAG-2005-09, ITCC-003, EU-20617, CCLG-CPP-05-07, ROCHE-MO18461, EUDRACT-2004-005247-10
Study First Received: August 3, 2006
Last Updated: September 19, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
untreated childhood brain stem glioma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
recurrent childhood ependymoma
recurrent childhood medulloblastoma
recurrent childhood supratentorial primitive neuroectodermal tumor
recurrent childhood visual pathway and hypothalamic glioma
childhood central nervous system germ cell tumor
childhood choroid plexus tumor
childhood craniopharyngioma
childhood grade I meningioma
childhood grade II meningioma
childhood grade III meningioma
childhood low-grade cerebral astrocytoma
childhood infratentorial ependymoma
childhood supratentorial ependymoma
recurrent childhood brain tumor
recurrent childhood subependymal giant cell astrocytoma
recurrent childhood pineoblastoma

Additional relevant MeSH terms:
Brain Neoplasms
Glioma
Nervous System Neoplasms
Central 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 July 26, 2014