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Treatment of Children and Adolescents With Diffuse Intrinsic Pontine Glioma and High Grade Glioma


Phase 3
3 Years
18 Years
Open (Enrolling)
Both
Brain and Central Nervous System Tumors

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Trial Information

Treatment of Children and Adolescents With Diffuse Intrinsic Pontine Glioma and High Grade Glioma


OBJECTIVES:

Primary

- Determine if the addition of high-dose methotrexate prior to standard treatment
improves survival of patients with malignant high-grade glioma or diffuse intrinsic
pontine glioma as compared to standard treatment only.

Secondary

- Determine if the addition of high-dose methotrexate, as compared to standard treatment
only, improves the tumor response of these patients.

- Determine if high-dose methotrexate, compared to standard treatment only, improves the
progression-free or event-free survival of these patients.

- Determine if high-dose methotrexate, as compared to standard treatment only, improves
the health status (quality of life) of these patients.

- Determine if consolidation therapy improves the overall, progression-free, or
event-free survival rates as compared to the historical control group.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified
according to tumor location includes pons (yes vs no) and complete or nearly complete
resection (yes vs no).

- Surgery: All patients are encouraged to undergo radical resection of the tumor to
reduce intracranial pressure, remove as much tumor tissue as possible, and obtain tumor
tissue for histological diagnosis. Within 14 days after surgery, patients proceed to
induction chemotherapy.

- Induction therapy: Patients are randomized to 1 of 2 treatment arms.

- Arm I:

- High-dose methotrexate with leucovorin calcium: Patients receive high-dose
methotrexate IV over 24 hours on days 1 and 15 and leucovorin calcium IV
every 6 hours on days 2-3 an 16-17. Patients proceed to chemoradiotherapy 4
weeks later.

- Chemoradiotherapy (course 1): Patients undergo external beam radiotherapy
once daily, 5 days a week, for approximately 6 weeks. Beginning on the first
day of radiotherapy, patients receive cisplatin IV over 1 hour on days 1-5,
etoposide IV over 2 hours on days 1-3, and vincristine IV on days 5, 12, 19,
26, and 33. Patients proceed to course 2 of chemoradiotherapy 7 days prior to
completion of radiotherapy.

- Chemoradiotherapy (course 2): Patients receive ifosfamide IV over 1 hour and
cisplatin IV over 1 hour on days 1-5, etoposide IV over 2 hours on days 1-3,
and vincristine IV on day 5. Patients proceed to consolidation chemotherapy 4
weeks later.

- Arm II: Patients receive chemoradiotherapy courses 1 and 2 as in arm I and proceed
to consolidation chemotherapy 4 weeks later.

- Consolidation chemotherapy: Patients receive vincristine IV on days 1, 8, and 15, oral
lomustine once on day 2, and oral prednisone once daily on days 1-17. Treatment repeats
every 6 weeks for up to 8 courses.

Quality of life is assessed 1 week after surgery, after completion of chemoradiotherapy, at
1, 4, and 13 months after completion of consolidation chemotherapy, and then annually for 3
years.

After completion of study treatment, patients are followed periodically for 3 years.

PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Newly diagnosed tumors of the brain or spinal cord, meeting one of the following
criteria:

- Histologically* confirmed diagnosis of 1 of the following high-grade gliomas:

- Glioblastoma (WHOº IV)

- Anaplastic astrocytoma (WHOº III)

- Gliosarcoma (WHOº III or IV)

- Anaplastic oligo-astrocytoma NOTE: *Histological requirement may be waived
for other types of brainstem glioma

- Radiologically proven diffuse intrinsic pontine glioma

- Second malignancy or disseminate metastases or multifocal tumors are allowed if the
field of irradiation is not too large

- No diffuse metastases making craniospinal irradiation necessary

PATIENT CHARACTERISTICS:

- No cardiorespiratory insufficiency requiring medical respiration

- No low blood pressure requiring systemic catecholamines

- No severe neurological damage (e.g., coma)

- No tetraplegia without possibility to communicate

- No other poor clinical condition

- Not pregnant

- Fertile patients must use effective contraception

- No hypersensitivity to methotrexate, cisplatin, vincristine, lomustine, or ifosfamide

- No other malignancy preceding radiotherapy that does not allow further radiation

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy for brain tumor

- The following prior therapies are allowed:

- Mistletoe

- H15 (extract of Boswellia serrata)

- Homeopathy therapy with dilution > 4D

- Alternative medicine without proven efficacy

- No prior radiotherapy for brain tumor

- No concurrent alcohol or tobacco consumption

- No concurrent participation in another study

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival (OS) rate at 5.5 years

Safety Issue:

No

Principal Investigator

Christoph Kramm, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University Children's Hospital

Authority:

United States: Federal Government

Study ID:

CDR0000454723

NCT ID:

NCT00278278

Start Date:

September 2003

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • untreated childhood brain stem glioma
  • untreated childhood cerebellar astrocytoma
  • childhood high-grade cerebral astrocytoma
  • childhood spinal cord neoplasm
  • Glioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms

Name

Location

M. D. Anderson Cancer Center at University of Texas Houston, Texas  77030-4009