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Samarium Sm 153 and Stem Cell Transplant Followed By Radiation Therapy Patients With Osteosarcoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00245011
First received: October 25, 2005
Last updated: May 27, 2014
Last verified: May 2014

October 25, 2005
May 27, 2014
October 2004
October 2008   (final data collection date for primary outcome measure)
Tumor response [ Time Frame: 1 week after study treatment ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00245011 on ClinicalTrials.gov Archive Site
  • Predictive value of imaging studies [ Time Frame: At Time of Tumor Resection ] [ Designated as safety issue: No ]
  • Overall and progression-free survival after study treatment [ Time Frame: Continual ] [ Designated as safety issue: No ]
  • Toxicity at end of study treatment [ Time Frame: Continual and at End of Study ] [ Designated as safety issue: Yes ]
  • Long term side effects of infusional samarium-153 after study treatment [ Time Frame: Continual ] [ Designated as safety issue: Yes ]
  • Correlative dose of radiation by low dose and high dose samarium-153 [ Time Frame: completion of treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Samarium Sm 153 and Stem Cell Transplant Followed By Radiation Therapy Patients With Osteosarcoma
High Dose Samarium-153 With Peripheral Blood Stem Cell Support in High Risk Osteogenic Sarcoma

RATIONALE: Radioactive drugs, such as samarium Sm 153 lexidronam pentasodium, may carry radiation directly to tumor cells and not harm normal cells. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and samarium Sm 153 lexidronam pentasodium. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving samarium Sm 153 lexidronam pentasodium together with a peripheral stem cell transplant and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving samarium Sm 153 lexidronam pentasodium together with autologous stem cell transplant and radiation therapy works in treating patients with recurrent or refractory, metastatic, or unresectable osteosarcoma.

OBJECTIVES:

Primary

  • Determine the clinical response in patients with recurrent or refractory, metastatic, or unresectable osteosarcoma treated with high-dose samarium Sm 153 lexidronam pentasodium (^153Sm-EDTMP) and autologous peripheral blood stem cell transplantation followed by external-beam radiotherapy.
  • Correlate the amount of radiation delivered to a tumor with low-dose ^153Sm-EDTMP with that of high-dose ^153Sm-EDTMP in patients treated with this regimen.

Secondary

  • Determine the overall and progression-free survival of patients treated with this regimen.
  • Determine the toxicity of this regimen in these patients.
  • Determine the long-term effects of this regimen in these patients.
  • Determine the predictive value of fludeoxyglucose F 18 positron emission tomography (FDG-PET), diffusion-weighted MRI, and magnetic resonance spectroscopy for evaluation of treatment response in patients treated with this regimen.

OUTLINE: Patients are stratified according to resectability of the primary tumor (recurrent, refractory, or very high-risk disease vs unresectable primary tumor).

  • Mobilization and collection of autologous peripheral blood stem cells (PBSCs)* : Patients receive ifosfamide IV daily for 5 days followed by filgrastim (G-CSF) subcutaneously daily. Patients then undergo leukapheresis for collection of autologous PBSCs until ≥ 2 x 10^6 CD34-positive cells/kg are collected.

NOTE: *Patients who have undergone PBSC collection before study entry proceed to high-dose samarium Sm 153 lexidronam pentasodium (153Sm-EDTMP) infusion without mobilization and collection of autologous PBSCs.

  • 153Sm-EDTMP infusion: Patients receive a trace dose of ^153Sm-EDTMP** IV over 1-2 minutes and undergo bone scan 4, 24, and 48-72 hours later. Six weeks later, patients receive high-dose ^153Sm-EDTMP IV over 1-2 minutes and undergo repeat bone scans 4, 24, and 48-72 hours later.

NOTE: **Patients may receive the trace dose on protocol JHOC-J0094.

  • Autologous peripheral blood stem cell transplantation (PBSCT): Between 12-14 days after administration of high-dose ^153Sm-EDTMP, patients undergo autologous PBSCT. Beginning 2 days later, patients receive G-CSF IV daily.
  • External-beam radiotherapy: Patients then undergo external-beam radiotherapy to the sites of bulky disease.
  • Surgery: Some patients may also undergo surgical resection of residual disease. After completion of study treatment, patients are followed periodically for up to 3 years.

PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Sarcoma
  • Biological: filgrastim
    Filgrastim will be administered every day until count recovery
  • Drug: ifosfamide
    Ifosfamide was administered as part of Stem Cell transplant prep.
  • Procedure: peripheral blood stem cell transplantation
    Before administration of Samarium, collection of autologous hematopoietic stem cells
  • Radiation: radiation
    Radiation Dosimetry performed at 4, 24, 48, and 72 after each infusion of Sm-EDTMP.
  • Radiation: samarium Sm 153 lexidronam pentasodium
    First dose of Sm-EDTMP administered after autologous stem cell collection. Second, higher dose, of SM-EDTMP administered after count recover. 14 days after administration of higher dose, patient undergoes autologous stem cell infusion.
Experimental: Samarium-153/Stem Cell Transplant/Radiation
Samarium Sm153 Lexidronam Pentasodium/Stem Cell Transplant/Radiation arm will receive Ifosphamide IV in preparation for peripheral blood stem cell transplant followed by collection of stem cells. Samarium Sm153 Lexidronam Pentasodium is administered after collection of peripheral blood stem cells. Once counts recover, while receiving filgrastim daily, a second, higher dose of Samarium-153 is given, followed in 14 days by infusion of the stem cells.
Interventions:
  • Biological: filgrastim
  • Drug: ifosfamide
  • Procedure: peripheral blood stem cell transplantation
  • Radiation: radiation
  • Radiation: samarium Sm 153 lexidronam pentasodium

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
11
March 2009
October 2008   (final data collection date for primary outcome measure)
  • Diagnosis of osteosarcoma

    • High-risk disease, meeting 1 of the following criteria:

      • Recurrent disease
      • Refractory to conventional therapy
      • Newly diagnosed metastatic disease with ≥ 4 pulmonary nodules or multiple bone lesions
      • Unresectable primary tumor
    • Prior intralesional resection allowed
  • Measurable disease by technetium Tc 99m diphosphonate bone scan
  • Refractory to all standard therapies or highly unlikely to respond to conventional treatment
  • Performance status Karnofsky 60-100%
  • Life expectancy more than 8 weeks
  • Absolute neutrophil count > 500/mm^3
  • Platelet count > 50,000/mm^3
  • Creatinine clearance > 70 mL/min OR * Radioisotope glomerular filtration rate normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Recovered from prior chemotherapy
  • No prior radiotherapy to the site of currently active disease
  • Concurrent enrollment on protocol JHOC-J0094 allowed
Both
13 Years to 50 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00245011
J0347 CDR0000447134, JHOC-J0347, JHOC-03090802
Yes
Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: David M. Loeb, MD, PhD Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
May 2014

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