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 - Full Text View

Sponsors and Collaborators:	Sidney Kimmel Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00245011

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 therapy Radiation: samarium Sm 153 lexidronam pentasodium	Phase II

MedlinePlus related topics: Cancer Radiation Therapy Soft Tissue Sarcoma

Drug Information available for: Filgrastim Samarium Sm 153 lexidronam pentasodium Quadramet Ifosfamide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	High Dose Samarium-153 With Peripheral Blood Stem Cell Support in High Risk Osteogenic Sarcoma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Tumor response beginning 1 week after study treatment [ Designated as safety issue: No ]
Correlate dose of radiation by low dose and high dose samarium-153 delivered to the tumor at the completion of treatment [ Designated as safety issue: No ]

Secondary Outcome Measures:

Predictive value of imaging studies at time of tumor resection [ Designated as safety issue: No ]
Overall and progression-free survival after study treatment [ Designated as safety issue: No ]
Toxicity at end of study treatment [ Designated as safety issue: Yes ]
Long term side effects of infusional samarium-153 after study treatment [ Designated as safety issue: Yes ]

Estimated Enrollment:	54
Study Start Date:	October 2004
Estimated Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

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

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

Contacts and Locations

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

National Cancer Institute (NCI)

Investigators

Principal Investigator:

David M. Loeb, MD, PhD

Sidney Kimmel Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( David M. Loeb )
Study ID Numbers:	CDR0000447134, JHOC-J0347, JHOC-03090802
Study First Received:	October 25, 2005
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00245011 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent osteosarcoma
metastatic osteosarcoma
localized osteosarcoma

Study placed in the following topic categories:

Osteosarcoma
Recurrence
Neoplasms, Connective and Soft Tissue
Malignant Mesenchymal Tumor
Soft Tissue Sarcomas
Ifosfamide
Analgesics, Non-Narcotic
Samarium ethylenediaminetetramethylenephosphonate

Sarcoma
Osteogenic Sarcoma
Peripheral Nervous System Agents
Antineoplastic Agents, Alkylating
Analgesics
Alkylating Agents
Isophosphamide mustard

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Osteosarcoma
Pharmacologic Actions
Neoplasms, Connective and Soft Tissue
Neoplasms
Ifosfamide
Neoplasms, Bone Tissue
Sensory System Agents

Analgesics, Non-Narcotic
Therapeutic Uses
Samarium ethylenediaminetetramethylenephosphonate
Sarcoma
Peripheral Nervous System Agents
Analgesics
Neoplasms, Connective Tissue
Antineoplastic Agents, Alkylating
Central Nervous System Agents
Alkylating Agents

ClinicalTrials.gov processed this record on May 07, 2009