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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2008 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00278278
First received: January 16, 2006
Last updated: December 18, 2013
Last verified: November 2008
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: cisplatin
Drug: etoposide
Drug: ifosfamide
Drug: lomustine
Drug: methotrexate
Drug: prednisone
Drug: vincristine sulfate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Children and Adolescents With Diffuse Intrinsic Pontine Glioma and High Grade Glioma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival (OS) rate at 5.5 years [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparison of OS, progression-free survival, and event-free survival with historical control annually [ Designated as safety issue: No ]
  • Long-term sequelae annually [ Designated as safety issue: No ]
  • Tumor response [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Event-free survival [ Designated as safety issue: No ]
  • Health status [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: September 2003
Estimated Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: cisplatin
Given IV
Drug: etoposide
Given IV
Drug: ifosfamide
Given IV
Drug: lomustine
Given IV
Drug: methotrexate
Given IV
Drug: prednisone
Given IV
Drug: vincristine sulfate
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: cisplatin
Given IV
Drug: etoposide
Given IV
Drug: ifosfamide
Given IV
Drug: lomustine
Given IV
Drug: prednisone
Given IV
Drug: vincristine sulfate
Given IV

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.

  Eligibility

Ages Eligible for Study:   3 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00278278

Locations
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
Gesellschaft fur Padiatrische Onkologie und Hamatologie - Germany
Investigators
Study Chair: Christoph Kramm, MD University Children's Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Christoph Kramm, University Children's Hospital
ClinicalTrials.gov Identifier: NCT00278278     History of Changes
Other Study ID Numbers: CDR0000454723, GPOH-HIT-GBM-D, EU-205100
Study First Received: January 16, 2006
Last Updated: December 18, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
untreated childhood brain stem glioma
untreated childhood cerebellar astrocytoma
childhood high-grade cerebral astrocytoma
childhood spinal cord neoplasm

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Nervous System Diseases
Etoposide phosphate
Isophosphamide mustard
Cisplatin
Etoposide
Methotrexate
Vincristine
Ifosfamide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Dermatologic Agents
Folic Acid Antagonists
Immunosuppressive Agents

ClinicalTrials.gov processed this record on September 22, 2014