Brain and Central Nervous System TumorsPhase 1NCT00360854
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
A Phase 1 study testing erlotinib hydrochloride, mutation analysis and polymorphism analysis in people with Brain and Central Nervous System Tumors, run by Children's Cancer and Leukaemia Group at 21 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- erlotinib hydrochloride, mutation analysis and polymorphism analysis
- Type of treatment
- Surgery or procedure
- How many people
- 48 participants
- Where
- 21 sitesin 2 countries
- Study dates
- May 2005to not given
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
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
Trial locations and contacts
21 sites in 2 countries.
21 sites in 2 countries
United Kingdom20 sites
Royal Aberdeen Children's Hospital
Aberdeen, Scotland, AB25 2ZG
Royal Belfast Hospital for Sick Children
Belfast, Northern Ireland, BT12 6BE
Birmingham Children's Hospital
Birmingham, England, B4 6NH
Institute of Child Health at University of Bristol
Bristol, England, BS2 8AE
Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
Cambridge, England, CB2 2QQ
Childrens Hospital for Wales
Cardiff, Wales, CF14 4XW
Royal Hospital for Sick Children
Edinburgh, Scotland, EH9 1LF
Royal Hospital for Sick Children
Glasgow, Scotland, G3 8SJ
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, LS9 7TF
Leicester Royal Infirmary
Leicester, England, LE1 5WW
Royal Liverpool Children's Hospital, Alder Hey
Liverpool, England, L12 2AP
Middlesex Hospital
London, England, W1T 3AA
Great Ormond Street Hospital for Children NHS Trust
London, England, WC1N 3JH
Central Manchester and Manchester Children's University Hospitals NHS Trust
Manchester, England, M27 4HA
Sir James Spence Institute of Child Health
Newcastle upon Tyne, England, NE1 4LP
Queen's Medical Centre
Nottingham, England, NG7 2UH
Oxford Radcliffe Hospital
Oxford, England, 0X3 9DU
Children's Hospital - Sheffield
Sheffield, England, S10 2TH
Southampton University Hospital NHS Trust
Southampton, England, SO16 6YD
Royal Marsden NHS Foundation Trust - Surrey
Sutton, England, SM2 5PT
About this study
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
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.
Read the 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.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- erlotinib hydrochloride, mutation analysis, polymorphism analysis, laboratory biomarker analysis, pharmacological study
- Keywords
- 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
- Medical subject headings
- Central Nervous System Neoplasms, Astrocytoma, Familial ependymoma, Medulloblastoma, Optic Nerve Glioma, Choroid Plexus Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
erlotinib hydrochlorideDrug
mutation analysisGenetic
polymorphism analysisGenetic
laboratory biomarker analysisOther
radiation therapyRadiation
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of erlotinib hydrochloride when given alone and in combination with radiotherapy
Secondary outcomes (5)
Dose-limiting toxicities
Safety
Pharmacokinetic behavior of erlotinib hydrocloride
Efficacy
Correlation of expression and mutations of epidermal growth factor receptor with treatment response
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2006 (estimated)
- Study startMay 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Cancer and Leukaemia Group
- Sponsor type
- University, hospital or other
- Investigators
- Darren Hargrave, MD, Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00360854
- Sponsor's protocol ID
- CDR0000481539
- Other IDs
- CCLG-NAG-2005-09, ITCC-003, EU-20617, CCLG-CPP-05-07, ROCHE-MO18461, EUDRACT-2004-005247-10
- Status last verified
- Jun 2007
- First submitted
- 3 Aug 2006
- Last updated
- 20 Sep 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00360854
- Acronym / sponsor ID
- CDR0000481539
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Children's Cancer and Leukaemia GroupUniversity, hospital or other
- Study start
- May 2005
- First posted
- 7 Aug 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| erlotinib hydrochloride | Drug | – |
| mutation analysis | Genetic | – |
| polymorphism analysis | Genetic | – |
| laboratory biomarker analysis | Other | – |
| pharmacological study | Other | – |
| radiation therapy | Radiation | – |
Primary outcome
Maximum tolerated dose of erlotinib hydrochloride when given alone and in combination with radiotherapy
5 secondary outcomes
Dose-limiting toxicities
Safety
Pharmacokinetic behavior of erlotinib hydrocloride
Efficacy
Correlation of expression and mutations of epidermal growth factor receptor with treatment response
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Darren Hargrave, MD
Royal Marsden NHS Foundation Trust
21 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing erlotinib hydrochloride, mutation analysis and polymorphism analysis in people with Brain and Central Nervous System Tumors, run by Children's Cancer and Leukaemia Group at 21 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United Kingdom, Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose of erlotinib hydrochloride when given alone and in combination with radiotherapy. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2013.