Samarium Sm 153 Lexidronam Pentasodium and Autologous Stem Cell Transplant Followed By Radiation Therapy in Treating Patients With Recurrent or Refractory, Metastatic, or Unresectable Osteosarcoma

• Tumor response [ Time Frame: 1 week after study treatment ] [ Designated as safety issue: No ]
• Correlate dose of radiation by low dose and high dose samarium-153 [ Time Frame: Completion of treatment ] [ Designated as safety issue: No ]

• 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 ]

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.

• 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.

• Senthamizhchelvan S, Hobbs RF, Song H, Frey EC, Zhang Z, Armour E, Wahl RL, Loeb DM, Sgouros G. Tumor dosimetry and response for 153Sm-ethylenediamine tetramethylene phosphonic acid therapy of high-risk osteosarcoma. J Nucl Med. 2012 Feb;53(2):215-24. Epub 2012 Jan 17.
• Loeb DM, Hobbs RF, Okoli A, Chen AR, Cho S, Srinivasan S, Sgouros G, Shokek O, Wharam MD Jr, Scott T, Schwartz CL. Tandem dosing of samarium-153 ethylenediamine tetramethylene phosphoric acid with stem cell support for patients with high-risk osteosarcoma. Cancer. 2010 Dec 1;116(23):5470-8. Epub 2010 Aug 16.
• Loeb DM, Garrett-Mayer E, Hobbs RF, Prideaux AR, Sgouros G, Shokek O, Wharam MD Jr, Scott T, Schwartz CL. Dose-finding study of 153Sm-EDTMP in patients with poor-prognosis osteosarcoma. Cancer. 2009 Jun 1;115(11):2514-22.

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

Performance status

• Karnofsky 60-100%

Life expectancy

• More than 8 weeks

Hematopoietic

• Absolute neutrophil count > 500/mm^3
• Platelet count > 50,000/mm^3

Hepatic

• Not specified

Renal

• Creatinine clearance > 70 mL/min OR
• Radioisotope glomerular filtration rate normal

Other

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

PRIOR CONCURRENT THERAPY:

Chemotherapy

• Recovered from prior chemotherapy

Radiotherapy

• No prior radiotherapy to the site of currently active disease

Surgery

• See Disease Characteristics

Other

• Concurrent enrollment on protocol JHOC-J0094 allowed