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
  Purpose

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.


Condition Intervention Phase
Sarcoma
Biological: filgrastim
Drug: ifosfamide
Procedure: peripheral blood stem cell transplantation
Radiation: radiation
Radiation: samarium Sm 153 lexidronam pentasodium
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: High Dose Samarium-153 With Peripheral Blood Stem Cell Support in High Risk Osteogenic Sarcoma

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Tumor response [ Time Frame: 1 week after study treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 11
Study Start Date: October 2004
Study Completion Date: March 2009
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   13 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • 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
  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: NCT00245011

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: David M. Loeb, MD, PhD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00245011     History of Changes
Other Study ID Numbers: J0347 CDR0000447134, JHOC-J0347, JHOC-03090802
Study First Received: October 25, 2005
Last Updated: May 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
recurrent osteosarcoma
metastatic osteosarcoma
localized osteosarcoma

Additional relevant MeSH terms:
Osteosarcoma
Sarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Ifosfamide
Isophosphamide mustard
Samarium ethylenediaminetetramethylenephosphonate
Lenograstim
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Adjuvants, Immunologic
Immunologic Factors

ClinicalTrials.gov processed this record on July 28, 2014