Clinical trial NCT00245011: Samarium Sm 153 and Stem Cell Transplant Followed By Radiation Therapy Patients With Osteosarcoma
Official title: High Dose Samarium-153 With Peripheral Blood Stem Cell Support in High Risk Osteogenic Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoma
Keywords: recurrent osteosarcoma
metastatic osteosarcoma
localized osteosarcoma
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-10-27
Enrollment: 11
Sex: ALL
Minimum age (years): 13
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 (cluster of differentiation 34)-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 (Johns Hopkins Oncology Center)-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 criteria: Inclusion

* 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
* Recovered from prior chemotherapy

Exclusion

* Pregnant or nursing
* Positive pregnancy test for females of childbearing potential
* Fertile patients do not agree to use effective contraception
* Prior radiotherapy to the site of currently active disease
* Concurrent enrollment on protocol JHOC-J0094 allowed

Primary outcomes:
measure: Tumor Response
timeFrame: 1 week after study treatment
Secondary outcomes:
measure: Predictive Value of Imaging Studies
timeFrame: At Time of Tumor Resection
measure: Overall and Progression-free Survival After Study Treatment
timeFrame: up to 4 years
measure: Toxicity at End of Study Treatment
timeFrame: Continual and at End of Study
measure: Long Term Side Effects of Infusional Samarium-153 After Study Treatment
timeFrame: Continual
measure: Correlative Dose of Radiation by Low Dose and High Dose Samarium-153
timeFrame: completion of treatment
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: David M. Loeb, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.2967/jnumed.111.096677. Epub 2012 Jan 17.
citation: 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. doi: 10.1002/cncr.25518. Epub 2010 Aug 16.
citation: 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. doi: 10.1002/cncr.24286.