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

Sponsor

Seattle Children's Hospital (Other)

Overall Status

Terminated

CT.gov ID

NCT00003194

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

65.6

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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: 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.

Condition or Disease	Intervention/Treatment	Phase
Unspecified Childhood Solid Tumor, Protocol Specific	Biological: filgrastim Drug: carboplatin Drug: cyclophosphamide Drug: etoposide Drug: thiotepa Drug: topotecan hydrochloride Procedure: peripheral blood stem cell transplantation	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Primary Purpose:

Treatment

Official Title:

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.

Study Start Date :

Jul 1, 1997

Actual Primary Completion Date :

Dec 19, 2002

Actual Study Completion Date :

Dec 19, 2002

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 30 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically proven recurrent or refractory pediatric solid tumor
Bone marrow metastases allowed

PATIENT CHARACTERISTICS:

Age:

1 to 30

Performance status:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105
2	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109-1024