Therapy for Children With Advanced Stage High Risk Neuroblastoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00186849
First received: September 12, 2005
Last updated: May 19, 2009
Last verified: May 2009
  Purpose

This is a Phase II pilot study of chemotherapy and surgery for children with advanced stage high-risk neuroblastoma utilizing topotecan during an upfront window and other active agents during induction and intensification phases. The primary purpose is to estimate the response rate to an upfront window of two cycles of intravenous topotecan. We hypothesize that the topotecan window will be an effective therapy in terms of the response rate.


Condition Intervention Phase
Neuroblastoma
Drug: Topotecan, Cyclophosphamide, Cisplatin, Doxorubicin, Etoposide, Ifosfamide, Carboplatin
Procedure: Peripheral Blood Stem Cell Transplant
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Therapy for Children With Advanced Stage High Risk Neuroblastoma

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Response rate [ Time Frame: 5 years ]

Secondary Outcome Measures:
  • Feasibility/toxicity of an intensification phase of high-dose chemotherapy with topotecan and cyclophosphamide followed by autologous peripheral blood stem cell transplant [ Time Frame: 5 years ]

Enrollment: 30
Study Start Date: October 1997
Study Completion Date: April 2001
Primary Completion Date: April 2001 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1 Drug: Topotecan, Cyclophosphamide, Cisplatin, Doxorubicin, Etoposide, Ifosfamide, Carboplatin
See Detailed Description section for details of treatment interventions.
Procedure: Peripheral Blood Stem Cell Transplant
See Detailed Description section for details of treatment interventions.

  Hide Detailed Description

Detailed Description:

In this prospective phase II trial, topotecan is administered intravenously daily for 5 days for each of 2 consecutive weeks for two cycles in an upfront treatment window. Patients subsequently will receive standard treatment during induction and intensification phases.

The objectives of this trial are:

  • To estimate the response rate to an upfront window of two cycles of IV topotecan when given in doses adjusted to attain a targeted systemic exposure in children with advanced stage neuroblastoma.
  • To determine the feasibility and toxicity of an intensification phase of high-dose chemotherapy with topotecan and cyclophosphamide followed by autologous peripheral blood stem cell transplant
  • To estimate the 3-year overall survival and progression-free survival in patients treated with this approach
  • To characterize the phenotype of neuroblastoma tumor cells
  • To evaluate the disposition of topotecan in previously untreated patients with neuroblastoma

Details for chemotherapy intervention:

Window Phase Topotecan description, window therapy-Topotecan given intravenously daily as a 30 minute infusion for five consecutive days, off two days, and then five consecutive days. The dose for day 1 and 2 was 3.0 mg/m2 and subsequent doses were adjusted to attain a target systemic exposure. A second course of Topotecan was given approximately 16 days from the end of the first cycle, with the initial dose for the second course of Topotecan based on the dose required in the preceding course to attain the target AUC.

Induction Phase

Cyclophosphamide, MESNA, Adriamycin, Cisplatin, Carboplatin, and Etoposide description, Induction Phase (after completion of window) consists of 4 cycles of therapy:

Cycle 1:Cyclophosphamide 1 gm/m2 daily x 2 I.V. day 1 and 2 Adriamycin 35 mg/m2 I.V. day 1 only, MESNA: 250 mg/m2 I.V. immediately following cyclophosphamide infusion and at 3 and 6 hours post-infusion, and Etoposide: 30 mg/m2 over 30 minutes, followed by 250 mg/m2/day x 3 days I.V. by continuous infusion (days 2-5) Cycles 2 and 4- Cisplatin 40 mg/m2/day x 5 I.V. over 1 hour (days 1-5) Etoposide 200 mg/m2/day x 3 I.V. over 1 hour (days 2,3,4) Cycle 3: Carboplatin: dose adapted from GFR on day 1. Dose in mg/m2 = 8 x [(0.93 GFR) + 15] Ifosfamide: 2 gm/m2 I.V. over 1 hour daily x 3 (days 2, 3, 4) MESNA: 500 mg/m2 I.V. immediately after ifosfamide and 3 and 6 hours later Etoposide: 100 mg/m2 IV daily x 3 over 1 hour (days 2, 3, 4).

Intensification Phase

Topotecan, Cyclophosphamide, and MESNA- Intensification Therapy:

Topotecan - targeted dose - daily x 5 days for two weeks. Cyclophosphamide 750 mg/m2 IV over 1 hour on days 8 through 12. MESNA 175 mg/m2 IV immediately after cyclophosphamide and 3 and 6 hours later. Infusion of previously collected peripheral blood stem cells on day 14.

Subjects that do not respond to the Topotecan window will not receive topotecan during intensification, but instead will receive the following intensification therapy:

Carboplatin 700 mg/m2/day IV, over one hour q.o.d. x 3 Etoposide 500 mg/m2/day IV, over 6 hours q.o.d. x 3. Infusion of previously collected peripheral blood stem cells on day 8

Details for Intervention: Procedure/Surgery: Surgery Surgical resection will be performed after the window therapy in feasible subjects. If surgery was not possible after the Topotecan window resection of the primary tumor mass and careful lymph node staging was done after recovery from induction and re-evaluation of tumor status.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Advanced stage,high-risk neuroblastoma
  • Histologic proof of neuroblastoma
  • Adequate renal function
  • ECOG performance status 0-2

Exclusion Criteria:

  • Previous therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00186849

Locations
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Wayne L. Furman, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Wayne L. Furman, MD / Principal Investigator, St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00186849     History of Changes
Other Study ID Numbers: NB-97
Study First Received: September 12, 2005
Last Updated: May 19, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Neuroblastoma

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cisplatin
Cyclophosphamide
Doxorubicin
Etoposide
Ifosfamide
Carboplatin
Topotecan
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on April 17, 2014