Clinical trial NCT00514397: Temozolomide and Radiation Therapy in Treating Young Patients With Pontine Glioma
Official title: A Phase II Multi-Centre Study of Concomitant and Prolonged Adjuvant Temozolomide With Radiotherapy in Diffuse Pontine Gliomas
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: untreated childhood brain stem glioma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-08-09
Enrollment: 43
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving temozolomide together with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving temozolomide together with radiation therapy works in treating young patients with pontine glioma.

Detailed description: OBJECTIVES:

Primary

* To evaluate the time to death in patients with newly diagnosed diffuse pontine gliomas, when treated with the combination of concomitant low-dose oral temozolomide and radiotherapy, followed by up to 12 months of maintenance therapy with extended low-dose temozolomide.
* To assess the quality of life of patients with diffuse pontine gliomas during and after treatment.

Secondary

* To evaluate the time to tumor progression in patients with newly diagnosed diffuse pontine gliomas, when treated with the combination of concomitant low-dose oral temozolomide and radiotherapy, followed by up to 12 months of maintenance therapy with extended low-dose temozolomide.
* To evaluate and document toxicities from the administration of temozolomide combined with radiotherapy and to further study any toxicities associated with the chronic administration of the extended low-dose temozolomide schedule in this population group.
* To document radiological response to the above treatment with MR imaging and, where available, functional imaging.

OUTLINE: This is a multicenter study.

* Chemoradiotherapy: Patients receive oral temozolomide once daily for 6 weeks (7 days per week) with concurrent radiotherapy (5 days per week).

Patients without evidence of disease progression proceed to maintenance therapy beginning at least 4 weeks after completion of radiotherapy.

* Maintenance therapy: Patients receive oral temozolomide daily on days 1-21. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed prior to chemoradiotherapy and prior to course 1 of adjuvant temozolomide and prior to every 3 subsequent courses of adjuvant temozolomide.

After completion of study therapy, patients are followed every 8 weeks.

Eligibility criteria: DISEASE CHARACTERISTICS:

Inclusion criteria:

* Newly diagnosed diffuse intrinsic lesion centered in the pons on MRI

  * No requirement for histological diagnosis
  * Clinical history \< 6 months
* Clinical findings must include at least 1 of the 3 following signs of brainstem tumor:

  * Cranial nerve deficit
  * Long tract signs
  * Ataxia

Exclusion criteria:

* Focal lesions of brainstem
* Predominantly exophytic tumors

PATIENT CHARACTERISTICS:

Inclusion criteria:

* Karnofsky performance status (PS) or Lansky PS 60-100% (unless reason for decrease in status is a direct result of neurological involvement of the brainstem glioma)
* Life expectancy \> 12 weeks
* Absolute neutrophil count ≥ 1,000/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 10 g/dL
* Urea and serum creatinine \< 1.5 times upper limit of normal (ULN)
* Total and direct bilirubin \< 1.5 times ULN
* AST and ALT \< 3 times ULN
* Negative pregnancy test within 7 days prior to administration of temozolomide for women of childbearing potential

Exclusion criteria:

* Frequent vomiting and/or medical condition, that could interfere with oral medication intake (e.g., partial bowel obstruction)
* Pregnant or breast-feeding women

PRIOR CONCURRENT THERAPY:

Exclusion criteria:

* Prior chemotherapy or radiotherapy
* Other concurrent investigational drugs
* Other concurrent chemotherapy, immunotherapy, or biologic therapy

Primary outcomes:
measure: Overall survival
measure: Quality of life including health status, behavior, and the subjective experience using HUI and SDQ methods
Secondary outcomes:
measure: Toxicity, steroid usage, and radiological response
measure: Adverse events, including abnormal laboratory parameters, as assessed by CTC criteria
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: Our Lady's Hospital for Sick Children Crumlin
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Children's Hospital, Alder Hey
state: England
city: London
country: United Kingdom
facility: University College Hospital
state: England
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
state: England
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Sir James Spence Institute of Child Health at Royal Victoria Infirmary
state: England
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre
state: England
city: Oxford
country: United Kingdom
facility: Oxford Radcliffe Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Children's Hospital - Sheffield
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Belfast
country: United Kingdom
facility: Royal Belfast Hospital for Sick Children
state: Northern Ireland
city: Aberdeen
country: United Kingdom
facility: Royal Aberdeen Children's Hospital
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Sick Children
state: Scotland
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Sick Children
state: Scotland
city: Cardiff
country: United Kingdom
facility: Childrens Hospital for Wales
state: Wales
Study officials:
affiliation: Sir James Spence Institute of Child Health at Royal Victoria Infirmary
name: Simon Bailey, MD
role: PRINCIPAL_INVESTIGATOR
References: