Temozolomide and Radiation Therapy in Treating Young Patients With Pontine Glioma

Brain and Central Nervous System Tumors Clinical Trial

Official title:

A Phase II Multi-Centre Study of Concomitant and Prolonged Adjuvant Temozolomide With Radiotherapy in Diffuse Pontine Gliomas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00514397
• Other study ID #: CCLG-CNS-2007-04
• Secondary ID: CDR0000560114EU-
• Status: Recruiting
• Phase: Phase 2
• First received: August 8, 2007
• Last updated: August 9, 2013
• Start date: January 2008

Study information

• Verified date: June 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 43
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 21 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• motexafin gadolinium

• temozolomide

Procedure:
• adjuvant therapy

• quality-of-life assessment

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Ireland	Our Lady's Hospital for Sick Children Crumlin	Dublin
United Kingdom	Royal Aberdeen Children's Hospital	Aberdeen	Scotland
United Kingdom	Royal Belfast Hospital for Sick Children	Belfast	Northern Ireland
United Kingdom	Birmingham Children's Hospital	Birmingham	England
United Kingdom	Bristol Royal Hospital for Children	Bristol	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Childrens Hospital for Wales	Cardiff	Wales
United Kingdom	Royal Hospital for Sick Children	Edinburgh	Scotland
United Kingdom	Royal Hospital for Sick Children	Glasgow	Scotland
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Royal Liverpool Children's Hospital, Alder Hey	Liverpool	England
United Kingdom	Great Ormond Street Hospital for Children	London	England
United Kingdom	University College Hospital	London	England
United Kingdom	Royal Manchester Children's Hospital	Manchester	England
United Kingdom	Sir James Spence Institute of Child Health at Royal Victoria Infirmary	Newcastle-Upon-Tyne	England
United Kingdom	Queen's Medical Centre	Nottingham	England
United Kingdom	Oxford Radcliffe Hospital	Oxford	England
United Kingdom	Children's Hospital - Sheffield	Sheffield	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Royal Marsden - Surrey	Sutton	England

Sponsors (1)

Lead Sponsor	Collaborator
Children's Cancer and Leukaemia Group

Countries where clinical trial is conducted

Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival			No
Primary	Quality of life including health status, behavior, and the subjective experience using HUI and SDQ methods			No
Secondary	Toxicity, steroid usage, and radiological response			Yes
Secondary	Adverse events, including abnormal laboratory parameters, as assessed by CTC criteria			Yes