Combination Chemotherapy Plus Peripheral Stem Cell Transplantation Followed by Surgery and/or Radiation Therapy in Treating Young Patients With Advanced Neuroblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00002740
Recruitment Status : Completed
First Posted : June 16, 2004
Last Update Posted : July 24, 2014
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief Summary:

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

Detailed Description:

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
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma

Arm Intervention/treatment
Experimental: Treatment - Carboplatin Chemotherapy
See detailed description.
Biological: filgrastim
Other Names:
  • G-CSF (Granulocyte colony stimulating factor
  • Neupogen
  • NSC# 614629

Drug: carboplatin
Other Names:
  • Cis-diamine [1,1-cyclobutane-dicarboxylato] platinum)
  • NSC# 241240

Drug: cyclophosphamide
Other Names:
  • Cytoxan
  • CTX
  • NSC# 26271

Drug: doxorubicin hydrochloride
Other Names:
  • Adriamycin
  • NSC #123127

Drug: etoposide
Other Names:
  • VP-16
  • NSC# 141540

Drug: mesna
Other Names:
  • Sodium 2-mercaptoethane sulfonate
  • NSC# 113891

Drug: vincristine sulfate
Other Names:
  • Oncovin
  • VCR
  • Leucocristine
  • NSC# 67474

Procedure: conventional surgery
Procedure: peripheral blood stem cell transplantation
Radiation: low-LET cobalt-60 gamma ray therapy
Radiation: low-LET photon therapy

Primary Outcome Measures :
  1. Event Free Survival
    Determine 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

DISEASE CHARACTERISTICS: Newly diagnosed stage IV neuroblastoma by one of the following: Histologic verification Demonstration of tumor cell clumps in bone marrow with elevated urinary catecholamine metabolites Initial presentation with low-stage disease allowed if followed by progression to stage IV disease

PATIENT CHARACTERISTICS: Age: 1 to 21 Performance status: Not specified Hematopoietic: (unless bone marrow involvement by tumor) Absolute neutrophil count greater than 1,000/mm3 Platelet count greater than 100,000/mm3 Hepatic: Bilirubin less than 3.0 mg/dL Renal: Creatinine less than 1.5 mg/dL Creatinine clearance or radionuclide GFR greater than 60 mL/min Cardiovascular: EKG normal Ejection fraction at least 55% by radionuclide MUGA OR Fractional shortening at least 28% by echocardiogram Other: No other significant organ dysfunction that precludes study treatment Body weight at least 10 kg Not pregnant or nursing Effective contraception required of fertile patients

PRIOR CONCURRENT THERAPY: No prior systemic chemotherapy No prior radiotherapy except as emergency treatment

Information from the National Library of Medicine

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 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
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Study Chair: Susan G. Kreissman, MD Duke Cancer Institute

Publications of Results:
Responsible Party: Children's Oncology Group Identifier: NCT00002740     History of Changes
Other Study ID Numbers: 3951
CCG-3951 ( Other Identifier: Children's Cancer Group )
CDR0000064656 ( Other Identifier: Clinical )
First Posted: June 16, 2004    Key Record Dates
Last Update Posted: July 24, 2014
Last Verified: July 2014

Keywords provided by Children's Oncology Group:
disseminated neuroblastoma

Additional relevant MeSH terms:
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Liposomal doxorubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors