Clinical trial NCT00005952: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Brain and Central Nervous System Tumors
Childhood Germ Cell Tumor
Head and Neck Cancer
Kidney Cancer
Neuroblastoma
Ovarian Cancer
Sarcoma
Testicular Germ Cell Tumor
Keywords: childhood low-grade cerebral astrocytoma
recurrent childhood rhabdomyosarcoma
childhood craniopharyngioma
disseminated neuroblastoma
stage 4S neuroblastoma
recurrent neuroblastoma
stage IV Wilms tumor
stage V Wilms tumor
recurrent Wilms tumor and other childhood kidney tumors
childhood central nervous system germ cell tumor
stage III malignant testicular germ cell tumor
recurrent malignant testicular germ cell tumor
stage IV nasopharyngeal cancer
recurrent nasopharyngeal cancer
childhood germ cell tumor
metastatic childhood soft tissue sarcoma
recurrent childhood soft tissue sarcoma
stage IV ovarian germ cell tumor
recurrent ovarian germ cell tumor
childhood high-grade cerebral astrocytoma
childhood oligodendroglioma
childhood choroid plexus tumor
untreated childhood brain stem glioma
recurrent childhood brain stem glioma
untreated childhood supratentorial primitive neuroectodermal tumor
recurrent childhood supratentorial primitive neuroectodermal tumor
untreated childhood cerebellar astrocytoma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
untreated childhood medulloblastoma
recurrent childhood medulloblastoma
untreated childhood visual pathway and hypothalamic glioma
recurrent childhood visual pathway and hypothalamic glioma
previously treated childhood rhabdomyosarcoma
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
newly diagnosed childhood ependymoma
recurrent childhood ependymoma
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 30
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall response at 12 months
measure: Disease-free survival at 12 months
Secondary outcomes:
measure: Toxicity by NCI Common Toxicity Criteria v. 3.0 at 12 months
measure: Engraftment related to autologous marrow or peripheral blood stem cell transplantation at 12 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Duke Cancer Institute
name: Henry S. Friedman, MD
role: STUDY_CHAIR
References: