Induction Chemotherapy Using Cyclophosphamide and Topotecan in Treating Patients Who Are Undergoing Autologous Peripheral Stem Cell Transplantation for Newly Diagnosed or Progressive Neuroblastoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00070200
First received: October 3, 2003
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Neuroblastoma
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
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 31
Study Start Date: March 2004
Study Completion Date: December 2013
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed neuroblastoma or ganglioneuroblastoma meeting 1 of the following staging criteria:

    • Newly diagnosed disease, at least 1 year of age, and meets criteria for 1 of the following:

      • International Neuroblastoma Staging System (INSS) stage 2a/2b with MYCN amplification (greater than 10) AND unfavorable pathology
      • INSS stage 3 with MYCN amplification OR unfavorable pathology
    • Newly diagnosed INSS stage 4 disease meeting criteria for 1 of the following:

      • Over 18 months of age
      • Age 12 to 18 months with any unfavorable biologic feature (MYCN amplification, unfavorable pathology, and/or DNA index=1) or any biologic feature that is indeterminant, unsatisfactory, or unknown

        • No INSS stage 4 disease and age 12 to 18 months with all 3 favorable biologic features (i.e., nonamplified MYCN, favorable pathology, and DNA index greater than 1)
    • Newly diagnosed INSS stage 3, 4, or 4S disease AND under 1 year of age with MYCN amplification
    • At least 1 year of age and initially diagnosed with INSS stage 1, 2, or 4S disease that progressed to stage 4 without interval chemotherapy

      • Must have been enrolled on COG-ANBL00B1 at initial diagnosis

PATIENT CHARACTERISTICS:

Age

  • 30 and under at initial diagnosis

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count at least 1,000/mm^3*
  • Platelet count at least 100,000/mm^3* (transfusion independent)
  • Hemoglobin at least 10.0 g/dL* (red blood cell transfusions allowed) NOTE: *Granulocytopenia, anemia, and/or thrombocytopenia allowed for patients with tumor metastatic to the bone marrow

Hepatic

  • Bilirubin no greater than 1.5 mg/dL
  • ALT less than 300 IU/L

Renal

  • Creatinine no greater than 1.5 mg/dL
  • Creatinine clearance or radioisotope glomerular filtration rate at least 60 mL/min

Cardiovascular

  • ECG normal
  • Shortening fraction at least 27% by echocardiogram OR
  • Ejection fraction at least 50% by MUGA

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • See Disease Characteristics
  • No more than 1 prior chemotherapy course on the low- or intermediate-risk neuroblastoma studies (COG-P9641, COG-A3961) prior to determination of MYCN amplification and Shimada histology

Endocrine therapy

  • Not specified

Radiotherapy

  • Prior localized emergency radiotherapy to sites of life-threatening or function-threatening disease allowed

Surgery

  • Not specified

Other

  • No other prior systemic therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00070200

Locations
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 Hospital
Westmead, New South Wales, Australia, 2145
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Julie R. Park, MD Seattle Children's Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00070200     History of Changes
Other Study ID Numbers: ANBL02P1, CDR0000330140, COG-ANBL02P1
Study First Received: October 3, 2003
Last Updated: February 12, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
recurrent neuroblastoma
stage 4S neuroblastoma
localized unresectable neuroblastoma
localized resectable neuroblastoma
regional neuroblastoma
disseminated 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
Cyclophosphamide
Liposomal doxorubicin
Doxorubicin
Vincristine
Topotecan
Isotretinoin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014