Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Recurrent or Refractory Solid Tumors

Study Overview
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Brief Summary
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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: Phase I trial to study the effectiveness of combination chemotherapy and peripheral stem cell transplantation in treating patients who have recurrent or refractory solid tumors.

Detailed Description
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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.

Official Title
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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.

Conditions
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Unspecified Childhood Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: filgrastim
* Drug: carboplatin
* Drug: cyclophosphamide
* Drug: etoposide
* Drug: thiotepa
* Drug: topotecan hydrochloride
* Procedure: peripheral blood stem cell transplantation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Drug: carboplatin|nan|
|Drug: cyclophosphamide|nan|
|Drug: etoposide|nan|
|Drug: thiotepa|nan|
|Drug: topotecan hydrochloride|nan|
|Procedure: peripheral blood stem cell transplantation|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified childhood solid tumor, protocol specific