Combination Chemotherapy and Radiation Therapy With or Without Methotrexate in Treating Young Patients With Newly Diagnosed Gliomas

December 18, 2013 updated by: Gesellschaft fur Padiatrische Onkologie und Hamatologie - Germany

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

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether giving methotrexate together with combination chemotherapy and radiation therapy is more effective than combination chemotherapy and radiation therapy alone in treating gliomas.

PURPOSE: This randomized phase III trial is studying giving methotrexate together with combination chemotherapy and radiation therapy to see how well it works compared to combination chemotherapy and radiation therapy alone in treating young patients with newly diagnosed gliomas.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

150

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I

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. Four weeks later, 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. Beginning seven days prior to completion of radiotherapy, 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.
Drug: methotrexate
Given IV
Drug: etoposide
Given IV
Drug: vincristine sulfate
Given IV
Drug: cisplatin
Given IV
Drug: ifosfamide
Given IV
Drug: prednisone
Given IV
Drug: lomustine
Given IV
Active Comparator: Arm II

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. Beginning seven days prior to completion of radiotherapy, 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.
Drug: etoposide
Given IV
Drug: vincristine sulfate
Given IV
Drug: cisplatin
Given IV
Drug: ifosfamide
Given IV
Drug: prednisone
Given IV
Drug: lomustine
Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall survival (OS) rate at 5.5 years

Secondary Outcome Measures

Outcome Measure
Progression-free survival
Event-free survival
Tumor response
Health status
Comparison of OS, progression-free survival, and event-free survival with historical control annually
Long-term sequelae annually

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gesellschaft fur Padiatrische Onkologie und Hamatologie - Germany

Investigators

  • Study Chair: Christoph Kramm, MD, University Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2003

Primary Completion (Anticipated)

March 1, 2010

Study Registration Dates

First Submitted

January 16, 2006

First Submitted That Met QC Criteria

January 16, 2006

First Posted (Estimate)

January 18, 2006

Study Record Updates

Last Update Posted (Estimate)

December 19, 2013

Last Update Submitted That Met QC Criteria

December 18, 2013

Last Verified

November 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000454723
  • GPOH-HIT-GBM-D
  • EU-205100

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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