Temozolomide Plus Lomustine Followed by Radiation Therapy in Treating Patients With High-Grade Malignant Glioma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00006024
First received: July 5, 2000
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining more than one chemotherapy drug with radiation therapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of temozolomide plus lomustine followed by radiation therapy in treating patients who have high-grade malignant glioma.


Condition Intervention Phase
Brain Tumor
Central Nervous System Tumor
Drug: lomustine
Drug: temozolomide
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Temozolomide and CCNU in Pediatric Patients With Newly Diagnosed Incompletely Resected Non-Brainstem High-Grade Gliomas

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]
    This trial is a phase I evaluation of temozolomide in combination with a fixed dose of CCNU with the starting dose for temozolomide


Enrollment: 32
Study Start Date: November 2000
Study Completion Date: September 2006
Primary Completion Date: January 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pre and Post radiation Chemotherapy Drug: lomustine Drug: temozolomide

Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose of temozolomide when administered with lomustine in patients with high-grade malignant gliomas.
  • Determine the dose-limiting toxic effects of this regimen in these patients.
  • Evaluate the feasibility of radiotherapy after this treatment regimen in this patient population.
  • Evaluate the radiographic responses in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of temozolomide.

Patients receive oral temozolomide on days 1-5 and oral lomustine on day 1. Treatment continues every 28 days, if blood counts have recovered, for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo radiotherapy on days 1-5 weekly for 6 weeks. Patients continue the same chemotherapy regimen for up to 6 more courses beginning 4 weeks after completion of radiotherapy.

Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed high-grade malignant glioma of one of the following subtypes:

    • Glioblastoma
    • Anaplastic astrocytoma
    • Anaplastic oligoastrocytoma
    • Gliomatosis cerebri
  • No disseminated disease or primary spinal cord malignancies
  • Measurable intracranial residual disease by MRI

PATIENT CHARACTERISTICS:

Age:

  • 3 and over
  • Under 22 at time of diagnosis

Performance status:

  • Karnofsky 50-100% if over 10 years of age
  • Lansky 50-100% if 10 years of age or under

Life expectancy:

  • At least 8 weeks

Hematopoietic:

  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 100,000/mm^3 (transfusion independent)
  • Hemoglobin at least 8.0 g/dL (RBC transfusions allowed)

Hepatic:

  • Bilirubin no greater than 1.5 times normal for age
  • SGPT no greater than 2.5 times normal for age
  • Albumin at least 2 g/dL

Renal:

  • Creatinine no greater than 1.5 times normal for age OR
  • Creatinine clearance or radioisotope glomerular filtration rate at least lower limit of normal for age

Pulmonary:

  • No dyspnea at rest
  • No exercise intolerance
  • Pulse oximetry at least 94%

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior biologic therapy
  • No concurrent prophylactic hematopoietic growth factors

Chemotherapy:

  • No prior chemotherapy

Endocrine therapy:

  • Prior corticosteroid therapy allowed
  • No concurrent corticosteroids as antiemetic

Radiotherapy:

  • No prior radiotherapy

Surgery:

  • No more than 31 days since prior maximal neurosurgical procedure

Other:

  • No concurrent phenobarbital or cimetidine
  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: NCT00006024

  Show 235 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Regina Jakacki, MD Children's Hospital of Pittsburgh of UPMC
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00006024     History of Changes
Other Study ID Numbers: ADVL0011, COG-ADVL0011, CCG-ADVL0011, CCG-A0993, CDR0000068036
Study First Received: July 5, 2000
Last Updated: February 11, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
childhood high-grade cerebral astrocytoma

Additional relevant MeSH terms:
Brain Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Glioma
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Lomustine
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 21, 2014