Temozolomide and Radiation Therapy in Treating Young Patients With Pontine Glioma

Condition(s) targeted: Brain and Central Nervous System Tumors

Intervention: motexafin gadolinium (Drug); temozolomide (Drug); adjuvant therapy (Procedure); quality-of-life assessment (Procedure); radiation therapy (Procedure)

Phase: Phase 2

Status: Recruiting

Sponsored by: Children's Cancer and Leukaemia Group

Official(s) and/or principal investigator(s):
Simon Bailey, MD, Principal Investigator, Affiliation: Sir James Spence Institute of Child Health

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.

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

Study design: Treatment, Non-Randomized

Primary outcome:

Overall survival

Quality of life including health status, behavior, and the subjective experience using HUI and SDQ methods

Secondary outcome:

Toxicity, steroid usage, and radiological response

Adverse events, including abnormal laboratory parameters, as assessed by CTC criteria

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.

Minimum age: 2 Years. Maximum age: 21 Years. Gender(s): Both.

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

Our Lady's Hospital for Sick Children Crumlin, Dublin 12, Ireland; Recruiting
Contact Person, Phone: 353-1-409-6659

Addenbrooke's Hospital, Cambridge, England CB2 2QQ, United Kingdom; Recruiting
Amos Burke, MD, Phone: 44-1223-348-151

Birmingham Children's Hospital, Birmingham, England B4 6NH, United Kingdom; Recruiting
Martin W. English, MD, Phone: 44-121-333-8412, Email: martin.english@bch.nhs.uk

Bristol Royal Hospital for Children, Bristol, England BS2 8AE, United Kingdom; Recruiting
Contact Person, Phone: 44-117-342-0205

Children's Hospital - Sheffield, Sheffield, England S10 2TH, United Kingdom; Recruiting
Contact Person, Phone: 44-114-271-7411

Great Ormond Street Hospital for Children, London, England WC1N 3JH, United Kingdom; Recruiting
Gill Levitt, MD, Phone: 44-20-7405-9200 ext. 0073

Leeds Cancer Centre at St. James's University Hospital, Leeds, England LS9 7TF, United Kingdom; Recruiting
Adam Glaser, MD, Phone: 44-113-206-4984, Email: adam.glaser@leedsth.nhs.uk

Leicester Royal Infirmary, Leicester, England LE1 5WW, United Kingdom; Recruiting
Johann Visser, MD, Phone: 44-116-258-5309, Email: johannes.visser@uhl-tr.nhs.uk

Oxford Radcliffe Hospital, Oxford, England 0X3 9DU, United Kingdom; Recruiting
Kate Wheeler, MD, Phone: 44-186-522-1066

Queen's Medical Centre, Nottingham, England NG7 2UH, United Kingdom; Recruiting
Contact Person, Phone: 44-115-823-0620

Royal Liverpool Children's Hospital, Alder Hey, Liverpool, England L12 2AP, United Kingdom; Recruiting
Contact Person, Phone: 44-151-252-5294

Royal Manchester Children's Hospital, Manchester, England M27 4HA, United Kingdom; Recruiting
Bernadette Brennan, MD, Phone: 44-161-922-2227, Email: bernadette.brennan@cmmc.nhs.uk

Royal Marsden - Surrey, Sutton, England SM2 5PT, United Kingdom; Recruiting
Contact Person, Phone: 44-20-8661-3455

Sir James Spence Institute of Child Health, Newcastle-Upon-Tyne, England NE1 4LP, United Kingdom; Recruiting
Contact Person, Phone: 44-191-202-3033 ext. 43028

Southampton General Hospital, Southampton, England SO16 6YD, United Kingdom; Recruiting
Janice A. Kohler, MD, FRCP, Phone: 44-23-8079-6942

University College Hospital, London, England NW1 2PCE, United Kingdom; Recruiting
Maria Michelagnoli, MD, Phone: 44-20-7380-9064, Email: maria.michelagnoli@uclh.nhs.uk

Royal Belfast Hospital for Sick Children, Belfast, Northern Ireland BT12 6BE, United Kingdom; Recruiting
Anthony McCarthy, MD, Phone: 44-289-063-3631, Email: anthonymcarthy@royalhospital.n.i.nhs.uk

Royal Aberdeen Children's Hospital, Aberdeen, Scotland AB25 2ZG, United Kingdom; Recruiting
Veronica Neefjes, Phone: 44-1224-550-217

Royal Hospital for Sick Children, Glasgow, Scotland G3 8SJ, United Kingdom; Recruiting
Milind D. Ronghe, MD, Phone: 44-141-201-9309

Royal Hospital for Sick Children, Edinburgh, Scotland EH9 1LF, United Kingdom; Recruiting
W. Hamish Wallace, MD, Phone: 44-131-536-0426

Childrens Hospital for Wales, Cardiff, Wales CF14 4XW, United Kingdom; Recruiting
Heidi Traunecker, MD, PhD, Phone: 44-29-2074-2285, Email: heidi.traunecker@cardiffandvale.wales.nhs.uk

Clinical trial summary from the National Cancer Institute's PDQ® database

Last updated: July 23, 2008