Intensive Chemo-Radiotherapy With Peripheral Blood Progenitor Cell Rescue for Children With Advanced Neuroblastoma and Sarcomas

This study has been completed.
Sponsor:
Collaborators:
Children's Hospital Boston
Children's Hospital of Philadelphia
Information provided by:
Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00165139
First received: September 9, 2005
Last updated: October 30, 2009
Last verified: October 2009
  Purpose

The main purpose of this study is to determine the short and long term side effects of a very intensive treatment, which includes combinations of chemotherapy drugs followed by radiation therapy and two transplants supported by peripheral blood progenitor cells (stem cells), for children with advanced stage neuroblastoma and sarcomas.


Condition Intervention Phase
Neuroblastoma
Ewings Sarcoma
Non-rhabdomyosarcoma Soft Tissue Sarcoma
Drug: Vincristine
Drug: Cyclophosphamide
Drug: Adriamycin
Drug: Etoposide (VP-16)
Drug: Cisplatin
Drug: Carboplatin
Drug: Melphalan
Drug: Ifosfamide
Drug: G-CSF (granulocyte-colony stimulating factor)
Drug: Mesna
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: Double Dose Intensive Chemo-Radiotherapy With Peripheral Blood Progenitor Cell Rescue for Children With Advanced Stage Neuroblastoma and Sarcomas

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • To determine the toxicity and feasibility of double dose chemo-radiotherapy with blood progenitor cell rescue in this patient population. [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Enrollment: 20
Study Start Date: January 1996
Study Completion Date: February 2009
Primary Completion Date: November 2000 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Vincristine
    Described under detailed description
    Drug: Cyclophosphamide
    Described under detailed description
    Drug: Adriamycin
    Described under detailed description
    Drug: Etoposide (VP-16)
    Described under detailed description
    Drug: Cisplatin
    Described under detailed description
    Drug: Carboplatin
    Described under detailed description
    Drug: Melphalan
    Described under detailed description
    Drug: Ifosfamide
    Described under detailed description
    Drug: G-CSF (granulocyte-colony stimulating factor)
    Described under detailed description
    Drug: Mesna
    Described under detailed description
Detailed Description:
  • The treatment is separated into three stages: 1) Initial treatment-chemotherapy and stem cell collection; 2) Treatment targeted directly to the main tumor-surgery and radiation therapy; 3) Intensified treatment: two stem cell transplants.
  • Patients will receive intensive treatment with a combination of seven drugs which will be given every 3 weeks, or as soon as the patient's blood counts are within safe limits. A total of 5 or 6 courses of chemotherapy will be given. The third and fourth course will be followed by stem cell collections and the last course will be followed by bone marrow harvest in preparation for transplant.
  • The first treatment involves a high-dose of Cisplatin intravenously once a day for 5 days and VP-16 intravenously on days 2,3 and 4 of the treatment.
  • The second course of treatment involves cyclophosphamide intravenously on day 1 and day 2, adriamycin intravenously continuously over 48 hours, and vincristine intravenously on day 1.
  • The third course of treatment involves ifosfamide daily on days 1-5 and VP-16 on days 1-3. Mesna will also be given to prevent bladder irritation.
  • During the fourth course patients will receive, carboplatin intravenously on days 1 and 2 and VP-16 on days 1,2 and 3 of treatment.
  • The fifth course of treatment will be identical to the second course.
  • G-CSF (granulocyte colony-stimulating factor) stimulates bone marrow to produce more white blood cells and will be given subcutaneously until the patients' white blood cell counts are at an acceptable level. This may require 10-14 days of G-CSF treatment.
  • After the first two treatments, and after the last course of treatment, patients will be evaluated for response. If significant tumor is still present in the bone marrow before the third treatment, stem cell collection will be delayed. If the bone marrow still shows disease after the next treatment, this plan of treatment will be stopped.
  • Patients may undergo surgery after the last treatment to remove the tumor and to evaluate the remaining disease. After recovery, radiation therapy may be performed to the main tumor area.
  • Patients will receive transplantations of stem cells twice during this study. After each preparative treatment, half of the patient's stored stem cells will be given intravenously. Until the stem cells restore safe levels of blood cells, the patient will be hospitalized (3-4 weeks or longer).
  • The first treatment will begin with high doses of carboplatin and VP-16 daily for 3 consecutive days followed by cyclophosphamide on the fourth and fifth days.
  • Between 4-6 weeks after the start of the first course of high dose chemotherapy a second course consisting of melphalan and total body irradiation (TBI) will be given. Melphalan will be given daily for 3 consecutive days followed by TBI twice a day for 3 days.
  • After each of the two high dose treatments outlined above, the stem cells that were previously harvested from the patient will be given back to them through a central line.
  • Stem cells will be collected on 3 separate occasions following each of two cycles of chemotherapy. They will then be processed using a technique that attempts to separate stem cells from other cells, including any cancer cells that may be present.
  • Bone marrow will also be harvested prior to the first transplant and will be used if blood counts do not recover after the stem cells are given.
  Eligibility

Ages Eligible for Study:   up to 19 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Previously untreated neuroblastoma Stage D > 365 days
  • Previously untreated neuroblastoma Stage C at age > 365 days with n-myc amplification
  • Previously untreated metastatic Ewings sarcoma/PNET
  • Previously untreated non-rhabdomyosarcoma soft tissue sarcoma
  • Confirmation of neuroblastoma at time of diagnosis by histologic specimen or with bone marrow specimen showing solid tumor. Confirmation of sarcoma by histologic specimen with evidence of metastatic disease be imaging study
  • Patient 19 years of age or younger
  • ANC > 1000
  • Platelet count > 75,000
  • SGOT < 2.5 x ULN
  • Normal serum creatinine levels for age

Exclusion Criteria:

  • Previous malignancy requiring nonsurgical treatment or bone marrow transplant.
  • Relapsed disease
  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: NCT00165139

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Children's Hospital Boston
Children's Hospital of Philadelphia
Investigators
Principal Investigator: Lisa Diller, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Lisa Diller, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00165139     History of Changes
Other Study ID Numbers: 94-131
Study First Received: September 9, 2005
Last Updated: October 30, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
Stem cell transplant
High-risk pediatric tumors

Additional relevant MeSH terms:
Sarcoma
Neuroblastoma
Sarcoma, Ewing
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Cyclophosphamide
Lenograstim
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
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on September 30, 2014