Induction Chemotherapy Using Cyclophosphamide and Topotecan in Treating Patients Who Are Undergoing Autologous Peripheral Stem Cell Transplantation for Newly Diagnosed or Progressive Neuroblastoma
RATIONALE: Drugs used in chemotherapy, such as topotecan and cyclophosphamide, use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects of induction chemotherapy using cyclophosphamide and topotecan in treating patients who are undergoing surgery and autologous stem cell transplantation followed by radiation therapy for newly diagnosed or progressive neuroblastoma.
Drug: doxorubicin hydrochloride
Drug: topotecan hydrochloride
Drug: vincristine sulfate
Procedure: conventional surgery
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Induction Regimen Incorporating Topotecan for Treatment of Newly Diagnosed High Risk Neuroblastoma|
- Proportion of patients who are classified as a "success" [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]Given that the documented delivered dose intensity of chemotherapy in current induction regimens is 75-85% of the intended dose intensity,5,78 we shall consider an individual patient as a "success" in terms of feasibility if the patient is able to receive 75% or more of the intended chemotherapy doses of known active agents.
- Number of toxic deaths [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]
- Proportion of patients with dose limiting toxicities during induction cycle 1 and 2 [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]Dose limiting toxicities during induction cycle 1 and 2 will be used to modify the topotecan dosage if necessary and to address Primary Aim 1 in a descriptive fashion.
- Tumor contamination of PBSCs [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]Tumor contamination of PBSCs as measured by immunohistochemical analysis following cycle 2 induction;
- Inability to adequately mobilize PBSCs [ Time Frame: Length of study ] [ Designated as safety issue: No ]Inability to adequately mobilize PBSCs, defined as a harvest of < 1.5 x 10 6 CD 34 cells/kg. A patient will be designated a PBSCs "failure" if either a) or b) is the case.
- Assessment of response [ Time Frame: Length of study ] [ Designated as safety issue: No ]After completion of induction therapy. Response will be determined using the International Response Criteria defined elsewhere in the protocol. The tumor response rate will be defined as the proportion of patients who achieve a CR, VGPR, or PR after completion of induction therapy.
|Study Start Date:||March 2004|
|Study Completion Date:||December 2013|
|Primary Completion Date:||September 2006 (Final data collection date for primary outcome measure)|
Experimental: All patients
Induction Cycles 1 and 2 (CT) (21 days each), Cyclophosphamide (Days 1 thru 5) weight based dosage (> 12 kg 400 mg/m2/day, < 12 kg 13.3 mg/kg/day, < 2 years old N/A. Topotecan (Days 1 thru 5) weight based dosage (> 12 kg 1.2 mg/m2/day, < 12 kg 0.04 mg/kg/day, < 2 years old 0.04 mg/kg/day). Filgrastim (Days 6 →) weight based dosage (> 12 kg 5 micrograms/kg, < 12 kg 5 micrograms /kg, < 2 years old 5 micrograms /kg.
|Biological: filgrastim Drug: cisplatin Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: isotretinoin Drug: melphalan Drug: topotecan hydrochloride Drug: vincristine sulfate Procedure: conventional surgery Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy|
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|United States, California|
|UCSF Comprehensive Cancer Center|
|San Francisco, California, United States, 94143-0106|
|United States, Illinois|
|Children's Memorial Hospital - Chicago|
|Chicago, Illinois, United States, 60614|
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|United States, Washington|
|Children's Hospital and Regional Medical Center - Seattle|
|Seattle, Washington, United States, 98105|
|Mary Bridge Children's Hospital and Health Center - Tacoma|
|Tacoma, Washington, United States, 98405|
|Australia, New South Wales|
|Westmead, New South Wales, Australia, 2145|
|Study Chair:||Julie R. Park, MD||Seattle Children's Hospital|