Combination Chemotherapy Plus Peripheral Stem Cell Transplantation Followed by Surgery and/or Radiation Therapy in Treating Young Patients With Advanced Neuroblastoma
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|ClinicalTrials.gov Identifier: NCT00002740|
Recruitment Status : Completed
First Posted : June 16, 2004
Last Update Posted : July 24, 2014
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow doctors to give higher doses of chemotherapy drugs and kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells.
PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation followed by surgery and/or radiation therapy in treating young patients who have newly diagnosed advanced neuroblastoma.
|Condition or disease||Intervention/treatment||Phase|
|Neuroblastoma||Biological: filgrastim Drug: carboplatin Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: mesna Drug: vincristine sulfate Procedure: conventional surgery Procedure: peripheral blood stem cell transplantation Radiation: low-LET cobalt-60 gamma ray therapy Radiation: low-LET photon therapy||Phase 1|
OBJECTIVES: I. Estimate the maximum tolerated dose of carboplatin that can be given in combination with cyclophosphamide (CTX) and etoposide following high dose CTX, doxorubicin, and vincristine in patients with newly diagnosed stage IV neuroblastoma. II. Determine the hematologic and nonhematologic toxic effects of this regimen in this patient population. III. Determine the change in neuroblastoma tumor cell content in peripheral blood stem cells (PBSC) collected following chemotherapy. IV. Assess the feasibility of repetitive collection, storage, and infusion of PBSC with multicycle high-dose chemotherapy in pediatric patients. V. Assess hematopoietic recovery following PBSC infusion as well as the CD34 content and CFU-GM yield of the PBSC products. VI. Assess the response rate and disease-free survival in the context of a phase I pilot study. VII. Determine the feasibility of administering twice-daily radiotherapy fractions to post-chemotherapy residual tumor volumes in neuroblastoma patients.
OUTLINE: This is a dose escalation study of carboplatin. Patients receive induction chemotherapy consisting of vincristine IV over 24 hours, cyclophosphamide IV over 4 hours, and doxorubicin IV over 24 hours on days 0, 1, 21, and 22. Patients receive filgrastim (G-CSF) subcutaneously (SQ) or IV beginning on days 3 and 24 and continuing until blood counts recover. Patients undergo peripheral blood stem cell (PBSC) collection after course 2 of induction chemotherapy. Patients receive G-CSF SQ or IV for 2 days prior to and during collection. PBSC are collected daily for 1-3 days. Patients may undergo autologous bone marrow collection after course 1 of consolidation therapy (after PBSC collection). Following mobilization, patients receive consolidation chemotherapy consisting of etoposide IV over 4 hours on days 0, 1, and 2 and carboplatin IV over 1 hour and cyclophosphamide IV over 4 hours on days 0 and 1. Patients receive G-CSF SQ or IV beginning on day 3 (within 4 hours of PBSC infusion) and continuing until blood counts recover. Patients receive PBSC reinfusion at 48-72 hours following completion of each chemotherapy course. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Upon recovery from consolidation chemotherapy, patients with no disease progression undergo tumor resection with or without radiotherapy. Patients undergoing radiotherapy receive therapy twice daily over 7 days. Patients with no disease progression, less than 2% detectable bone marrow disease, and adequate bone marrow cellularity may undergo additional therapy consisting of autologous bone marrow transplantation per appropriate transplant protocol. Cohorts of 6-12 patients receive escalating doses of carboplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience dose limiting toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 24-30 patients will be accrued for this study within approximately 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Official Title:||Phase I Pilot Study of Multiple Cycles of High Dose Chemotherapy With Peripheral Blood Stem Cell Infusions In Advanced Stage Neuroblastoma|
|Study Start Date :||May 1996|
|Actual Primary Completion Date :||March 2004|
|Actual Study Completion Date :||September 2005|
Experimental: Treatment - Carboplatin Chemotherapy
See detailed description.
Drug: doxorubicin hydrochloride
Drug: vincristine sulfate
Procedure: conventional surgery
Procedure: peripheral blood stem cell transplantation
Radiation: low-LET cobalt-60 gamma ray therapy
Radiation: low-LET photon therapy
- Event Free SurvivalDetermine the maximum tolerated dose of a combination of cyclophosphamide, carboplatin, and etoposide for 3 consecutive courses following 2 cycles of a fixed dose of high dose cyclophosphamide, doxorubicin, and vincristine given on a 21 day schedule using G-CSF in combination with peripheral blood stem cells.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00002740
|United States, California|
|Children's Hospital Los Angeles|
|Los Angeles, California, United States, 90027-0700|
|UCSF Cancer Center and Cancer Research Institute|
|San Francisco, California, United States, 94115-0128|
|United States, Indiana|
|Indiana University Cancer Center|
|Indianapolis, Indiana, United States, 46202-5265|
|United States, Minnesota|
|University of Minnesota Cancer Center|
|Minneapolis, Minnesota, United States, 55455|
|United States, Ohio|
|Children's Hospital Medical Center - Cincinnati|
|Cincinnati, Ohio, United States, 45229-3039|
|Children's Hospital of Columbus|
|Columbus, Ohio, United States, 43205-2696|
|United States, Washington|
|Children's Hospital and Regional Medical Center - Seattle|
|Seattle, Washington, United States, 98105|
|Study Chair:||Susan G. Kreissman, MD||Duke Cancer Institute|