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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00002740
First received: November 1, 1999
Last updated: July 23, 2014
Last verified: July 2014

November 1, 1999
July 23, 2014
May 1996
March 2004   (final data collection date for primary outcome measure)
Event Free Survival [ Designated as safety issue: No ]
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.
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Complete list of historical versions of study NCT00002740 on ClinicalTrials.gov Archive Site
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Combination Chemotherapy Plus Peripheral Stem Cell Transplantation Followed by Surgery and/or Radiation Therapy in Treating Young Patients With Advanced Neuroblastoma
Phase I Pilot Study of Multiple Cycles of High Dose Chemotherapy With Peripheral Blood Stem Cell Infusions In Advanced Stage Neuroblastoma

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.

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.

Interventional
Phase 1
Primary Purpose: Treatment
Neuroblastoma
  • Biological: filgrastim
    Other Names:
    • G-CSF (Granulocyte colony stimulating factor
    • Neupogen
    • NSC# 614629
  • Drug: carboplatin
    Other Names:
    • CBDCA
    • 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
Experimental: Treatment - Carboplatin Chemotherapy
See detailed description.
Interventions:
  • 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
Bensimhon P, Villablanca JG, Sender LS, Matthay KK, Park JR, Seeger R, London WB, Yap JS, Kreissman SG. Peripheral blood stem cell support for multiple cycles of dose intensive induction therapy is feasible with little risk of tumor contamination in advanced stage neuroblastoma: a report from the Childrens Oncology Group. Pediatr Blood Cancer. 2010 Apr;54(4):596-602. doi: 10.1002/pbc.22344.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
September 2005
March 2004   (final data collection date for primary outcome measure)

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

Both
1 Year to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00002740
3951, CCG-3951, CDR0000064656
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Study Chair: Susan G. Kreissman, MD Duke Cancer Institute
Children's Oncology Group
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP