A Phase I Study of Thiotepa in Combination With Carboplatin and Topotecan With Peripheral Blood Progenitor Cell Support for the Treatment of Children With Recurrent or Refractory Solid Tumors.
1 Year
30 Years
Both
Unspecified Childhood Solid Tumor, Protocol Specific
Trial Information
A Phase I Study of Thiotepa in Combination With Carboplatin and Topotecan With Peripheral Blood Progenitor Cell Support for the Treatment of Children With Recurrent or Refractory Solid Tumors.
OBJECTIVES:
- Determine the maximum tolerated dose of thiotepa in combination with carboplatin and
topotecan with peripheral blood stem cell transplantation in patients with recurrent or
refractory pediatric solid tumors.
- Determine the toxicity of this regimen in these patients.
OUTLINE: This is a dose escalation study of thiotepa.
Patients may receive 2 courses of mobilization comprising cyclophosphamide and etoposide
with filgrastim (G-CSF) support and peripheral blood stem cell (PBSC) collection.
Patients receive thiotepa IV over 2 hours on days 0 and 1; topotecan IV over 30 minutes on
days 0-4; and carboplatin IV over 2 hours on days 2 and 3. Patients also receive G-CSF
beginning on day 5, 24-36 hours following the last dose of topotecan. PBSC are reinfused on
day 6 (36-48 hours following the last dose of topotecan) of each course of therapy. Patients
receive 3 courses of therapy.
Cohorts of 3-6 patients receive escalating doses of thiotepa until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6
patients experience dose-limiting toxicity.
Patients are followed at 1 and 2 years.
PROJECTED ACCRUAL: A maximum of 24 patients will be accrued into this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically proven recurrent or refractory pediatric solid tumor
- Bone marrow metastases allowed
PATIENT CHARACTERISTICS:
Age:
- 1 to 30
Performance status:
- 0-2
Life expectancy:
- At least 2 months
Hematopoietic:
- Absolute neutrophil count at least 1,000/mm3
- Platelet count at least 100,000/mm3 (transfusion independent)
- Hemoglobin at least 10 g/dL (RBC transfusion allowed)
Hepatic:
- Bilirubin no greater than 1.5 times normal
- SGOT no greater than 2.5 times normal
Renal:
- Adequate renal function as defined by one of the following:
- GFR by creatinine clearance
- Radioisotope GFR
- Iothalamate at least 70 mL/min
Cardiovascular:
- Adequate cardiac function as defined by one of the following:
- Ejection fraction at least 55% by MUGA
- Fractional shortening at least 28% by echocardiogram
Neurologic:
- Adequate CNS function as defined by:
- Seizure disorder, if present, controlled by anticonvulsants
- CNS toxicity no greater than grade 2
Other:
- No uncontrolled infections
- Not pregnant or nursing
- No allergy to platinum compounds
- No history of allergy to etoposide (unless mobilization phase not required)
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Recovered from prior immunotherapy
- At least 1 week since prior cytokines
- At least 3 months since prior bone marrow or peripheral blood stem cell
transplantation
- No concurrent immunomodulator
- No concurrent cytokines
Chemotherapy:
- At least 3 weeks (6 for nitrosourea) since prior chemotherapy and recovered
- No prior thiotepa
- No other concurrent chemotherapy
Endocrine therapy:
- Not specified
Radiotherapy:
- Recovered from prior radiotherapy
- At least 6 months since prior total body irradiation conditioning
- No concurrent radiotherapy to greater than 10% of total liver, lung, or bone marrow
Surgery:
- Not specified
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Douglas Hawkins, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Seattle Children's Hospital
Authority:
United States: Federal Government
Study ID:
CDR0000066029
NCT ID:
NCT00003194
Start Date:
July 1997
Completion Date:
Related Keywords:
- Unspecified Childhood Solid Tumor, Protocol Specific
- unspecified childhood solid tumor, protocol specific
- Neoplasms
Name | Location |
|---|---|
| Fred Hutchinson Cancer Research Center | Seattle, Washington 98109 |
| Children's Hospital and Regional Medical Center - Seattle | Seattle, Washington 98105 |
