Brief Title
Temozolomide Plus Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Malignant Glioma or Recurrent CNS or Other Solid Tumors
Official Title
A Phase I/II Trial of Temodar in Pediatric Patients and Young Adults With High-Risk or Recurrent Solid Tumors
Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation
may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of temozolomide
when given with peripheral stem cell transplantation and to see how well they work in
treating children with newly diagnosed malignant glioma or recurrent CNS tumors or other
solid tumors.
Detailed Description
OBJECTIVES:
- Determine the maximum tolerated dose of temozolomide in children with newly diagnosed
malignant glioma or recurrent CNS or other solid tumors.
- Evaluate the toxicity of this treatment in these patients.
- Determine the activity of this treatment in these patients.
OUTLINE: This is a dose escalation study of temozolomide.
Patients receive filgrastim (G-CSF) subcutaneously (SQ) or IV beginning on day -5 and
continuing through at least day 3. Peripheral blood stem cells (PBSC) are collected on days
0, 2, and 4. Patients then receive oral temozolomide daily for 5 consecutive days. PBSC
collections are reinfused 1 day after the last dose of temozolomide. Patients also receive
G-CSF beginning at the time of transplant and continuing until blood counts recover.
Treatment continues in the absence of disease progression or unacceptable toxicity.
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 at which 2 of 6 patients experience
dose limiting toxicities.
Patients are followed every 3 months for 1-3 years, then annually thereafter.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study over 12 months.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Overall response at 12 months
Secondary Outcome
Toxicity by NCI Common Toxicity Criteria v. 3.0 at 12 months
Condition
Brain and Central Nervous System Tumors
Intervention
filgrastim
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
30
Start Date
August 2000
Completion Date
November 2005
Primary Completion Date
November 2005
Eligibility Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed newly diagnosed malignant glioma or recurrent malignant CNS
tumor of any pathology OR
- Histologically confirmed non-CNS tumor
- Recurrent soft tissue sarcomas (e.g., rhabdomyosarcoma)
- Recurrent or resistant neuroblastoma
- Recurrent Wilm's tumor
- Recurrent Ewing's sarcoma
- Recurrent primitive neuroectodermal tumors
- Recurrent nasopharyngeal carcinoma
- Recurrent germ cell tumor
- Expected cure rate less than 10% with standard therapy
- Measurable and/or active disease
- History of bone marrow tumor infiltration with or without mass lesions or isolated
abnormal CSF cytology as only evidence of recurrent disease allowed if complete
response was first achieved with primary conventional therapy
PATIENT CHARACTERISTICS:
Age:
- 18 and under
Performance status:
- Karnofsky 70-100% OR
- Lansky 70-100%
Life expectancy:
- Greater than 8 weeks
Hematopoietic:
- Reasonably cellular bone marrow (greater than 15% cellularity on biopsy)
- Absolute neutrophil count greater than 1,000/mm^3
- Platelet count greater than 75,000/mm^3
Hepatic:
- Bilirubin less than 2.0 mg/dL
- SGPT less than 120 U/L
Renal:
- Creatinine less than 1.5 mg/dL
Cardiovascular:
- Systolic fraction or ejection fraction at least 80% predicted for age by
echocardiogram
Pulmonary:
- CVC or DLCO at least 60% predicted for age OR clearance from pulmonologist
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No active infection
- Able to tolerate vigorous hydration schedule
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- No concurrent white blood cell transfusion
- No other concurrent hematopoietic growth factors
Chemotherapy:
- See Disease Characteristics
- At least 4 weeks since prior chemotherapy
- No other concurrent cytotoxic drugs (systemic or intrathecal)
Endocrine therapy:
- Concurrent corticosteroids allowed
Radiotherapy:
- See Disease Characteristics
- At least 1 week since prior radiotherapy
Surgery:
- At least 1 week since prior surgery
Other:
- No other concurrent investigational agents
Gender
All
Ages
N/A - 18 Years
Accepts Healthy Volunteers
No
Contacts
Henry S. Friedman, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00005952
Organization ID
1735
Secondary IDs
DUMC-1735-04-9R5
Responsible Party
Sponsor
Study Sponsor
Duke University
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Henry S. Friedman, MD, Study Chair, Duke Cancer Institute
Verification Date
February 2013