Temozolomide Plus Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Malignant Glioma or Recurrent CNS or Other Solid Tumors

A Phase I/II Trial of Temodar in Pediatric Patients and Young Adults With High-Risk or Recurrent Solid Tumors

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.

Study Overview

• Status: Completed
• Conditions: Sarcoma; Kidney Cancer; Testicular Germ Cell Tumor; Head and Neck Cancer; Ovarian Cancer; Brain and Central Nervous System Tumors; Neuroblastoma; Childhood Germ Cell Tumor
• Intervention / Treatment: Drug: temozolomide; Procedure: peripheral blood stem cell transplantation; Biological: filgrastim

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall response at 12 months
Disease-free survival at 12 months

Secondary Outcome Measures

Outcome Measure
Toxicity by NCI Common Toxicity Criteria v. 3.0 at 12 months
Engraftment related to autologous marrow or peripheral blood stem cell transplantation at 12 months

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: August 1, 2000
• Primary Completion (Actual): November 1, 2005
• Study Completion (Actual): November 1, 2005

Study Registration Dates

• First Submitted: July 5, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): June 20, 2013
• Last Update Submitted That Met QC Criteria: June 19, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: stage III malignant testicular germ cell tumor; untreated childhood brain stem glioma; childhood high-grade cerebral astrocytoma; previously treated childhood rhabdomyosarcoma; recurrent childhood rhabdomyosarcoma; disseminated neuroblastoma; recurrent neuroblastoma; stage 4S neuroblastoma; untreated childhood medulloblastoma; untreated childhood cerebellar astrocytoma; newly diagnosed childhood ependymoma; recurrent ovarian germ cell tumor; stage IV ovarian germ cell tumor; recurrent malignant testicular germ cell tumor; stage IV Wilms tumor; stage V Wilms tumor; metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor; recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor; recurrent nasopharyngeal cancer; stage IV nasopharyngeal cancer; recurrent Wilms tumor and other childhood kidney tumors; childhood oligodendroglioma; recurrent childhood supratentorial primitive neuroectodermal tumor; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; recurrent childhood ependymoma; metastatic childhood soft tissue sarcoma; recurrent childhood soft tissue sarcoma; recurrent childhood brain stem glioma; recurrent childhood medulloblastoma; recurrent childhood visual pathway and hypothalamic glioma; childhood craniopharyngioma; childhood central nervous system germ cell tumor; childhood germ cell tumor; childhood choroid plexus tumor; childhood low-grade cerebral astrocytoma; untreated childhood supratentorial primitive neuroectodermal tumor; untreated childhood visual pathway and hypothalamic glioma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Neoplasms; Sarcoma; Neoplasms, Germ Cell and Embryonal; Nervous System Neoplasms; Central Nervous System Neoplasms; Neuroblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: 1735; DUMC-1735-04-9R5; DUMC-1735-02-9R3; DUMC-1735-01-9R2; DUMC-1833-99-10; NCI-G00-1796; CDR0000067932 (Other Identifier: NCI)