Osteosarcoma: Differentiation of Bone Sarcomas and Osteomyelitis With Ferumoxytol-Enhanced MRI

• Sponsor: Heike E Daldrup-Link (Other)
• Overall Status: Completed
• CT.gov ID: NCT01336803
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arm: 1
• Actual Duration (Months): 86
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This pilot trial studies the differentiation of bone sarcomas and osteomyelitis with ferumoxytol-enhanced magnetic resonance imaging (MRI). Imaging procedures that allow doctors to more accurately differentiate between malignant bone sarcomas and osteomyelitis may help in diagnosing patients correctly and may result in more timely treatment.

Condition or Disease	Intervention/Treatment	Phase
Bone Cancer; Chondrosarcoma; Ewing's Sarcoma; Osteosarcoma; Rhabdomyosarcoma; Bone Necrosis; Bone Sarcoma; Osteomyelitis	Drug: Feraheme; Procedure: Magnetic Resonance Imaging (MRI) scan	Phase 2

Detailed Description

BACKGROUND; In this study, T1, T2, and T2* represent parameters of magnetic resonance imaging (MRI).

The T1 relaxation time, also known as the spin-lattice relaxation time, is a measure of how quickly the net magnetization vector (NMV) recovers to its ground state in the direction of B0. T1 is assessed immediately post-contrast. A T1-weighted image (T1WI ) is one of the basic pulse sequences in MRI and demonstrates differences in the T1 relaxation times of tissues. A T1WI relies upon the longitudinal relaxation of a tissue's net magnetization vector (NMV).

T2 is a time constant for the decay of transverse magnetization arising from natural interactions at the atomic or molecular levels, and be considered the "natural" or "true" T2 of the tissue. However, in any nuclear magnetic resonance (NMR) experiment, transverse magnetization decays much faster than would be predicted by natural atomic and molecular mechanisms. Accordingly, T2 * is the time constant for the decay of transverse magnetization as observed in a tissue during a MRI scan, and be considered the"effective T2" (represented as T2*). T2* is always ≤ T2. In this study, T2 * is assessed after 24 hours.

OUTLINE:

Patients receive ferumoxytol intravenously (IV) and then undergo ferumoxytol-enhanced MRI up to 1 hour after infusion and up to 24 hours post-infusion.

PRIMARY OBJECTIVES:

• Establish magnetic resonance (MR) imaging characteristics of bone sarcomas and osteomyelitis based on their ferumoxytol-enhancement on relatively early post-contrast T1-weighted images.

• Establish MR imaging characteristics of bone sarcomas and osteomyelitis based on their ferumoxytol-enhancement on delayed postcontrast T2-weighted images.

• Establish T2-weighted MR imaging characteristics of iron-labeled mesenchymal stem cell (MSC) in osteonecrotic bone over time, before and after surgical core decompression and bone marrow implantation.

• Adding a second branch for patients who can not receive ferumoxytol but still getting the MRI exam.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Pilot Differentiation of Bone Sarcomas and Osteomyelitis With Ferumoxytol-Enhanced MRI
• Actual Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Oct 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Feraheme Intravenous injection of Feraheme, 5 mg Fe/kg	Drug: Feraheme; 5 mg/kg by intravenous (IV) administration; Other Names: ferumoxytol ; Procedure: Magnetic Resonance Imaging (MRI) scan; Standard of Care magnetic resonance imaging (MRI) scans using GE 1.5T and 3T MRI scanners/; Other Names: Magnetic Resonance (MR) scan

Outcome Measures

Primary Outcome Measures

1. T2* Relaxation Time of Bone Sarcomas and Osteomyelitis Subjects [24 hours]

   Differentiation of bone sarcomas and osteomyelitis with ferumoxytol-enhanced magnetic resonance imaging (MRI) was assessed as the difference of mean T2 * relaxation time of bone sarcoma and osteomyelitis subjects. The outcome is reported as the difference of the mean T2 * values, with standard deviation.

Secondary Outcome Measures

1. Differentiation of Bone Sarcomas Pre-ferumoxytol and Post-ferumoxytol Contrast [Baseline and Post-Treatment-24 hours]

   Differentiation of bone sarcomas pre-ferumoxytol and post-ferumoxytol contrast was assessed by difference of mean T2 * relaxation time pre-ferumoxytol and post-ferumoxytol contrast, in bone sarcoma subjects only.

2. Differentiation of Lymphoma and Bone Sarcomas With Ferumoxytol-enhanced MRI [24 hours]

   Differentiation of lymphoma from bone sarcoma was assessed as the difference of mean T2 * relaxation time determined by ferumoxytol-enhanced MRI. .

3. Differentiation of CD68-positive Tumor-associated Macrophages (TAM) in Lymphomas and Bone Sarcomas [24 hours]

   Differentiation of CD68-positive tumor-associated macrophages (TAM) between lymphoma and bone sarcoma was assessed as the difference of mean area density of CD68-positive TAM in those populations.

4. Differentiation of CD163-positive Tumor-associated Macrophages (TAM) in Lymphomas and Bone Sarcomas [24 hours]

   Differentiation of CD163-positive tumor-associated macrophages (TAM) between lymphoma and bone sarcoma was assessed as the difference of mean area density of CD163-positive TAM in those populations.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA

• Age 10 to 21 years

• Suspected or confirmed diagnosis of a bone sarcoma or osteomyelitis

• Informed consent with assent as appropriate.

EXCLUSION CRITERIA

• Contraindication to MRI

• Presence of metal implants

• Need for sedation or anesthesia

• Claustrophobia

• Hemosiderosis or hemochromatosis

• History of allergic reactions to similar compounds will be obtained and patients with positive history of allergic reactions will be excluded from the study

• Females who are pregnancy or nursing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Heike E Daldrup-Link

Investigators

• Principal Investigator: Heike E Daldrup-Link, MD, Stanford University
• Principal Investigator: Neyssa Marina, MD, Stanford University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 4, 2011

More Information

Publications

None provided.

• Responsible Party: Heike E Daldrup-Link, Professor of Radiology (General Radiology), Stanford University
• ClinicalTrials.gov Identifier: NCT01336803
• Other Study ID Numbers: IRB-20253(osteosarcoma); SU-04062011-7666; PEDSBONE0006
• First Posted: Apr 18, 2011
• Last Update Posted: Jun 18, 2019
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Osteomyelitis; Sarcoma; Osteosarcoma; Rhabdomyosarcoma; Sarcoma, Ewing; Chondrosarcoma; Bone Neoplasms; Osteonecrosis; Necrosis; Ferrosoferric Oxide

Study Results

Participant Flow

Arm/Group Title	Feraheme
Arm/Group Description	Intravenous injection of Feraheme, 5 mg Fe/kg Feraheme: 5 mg Fe/kg by intravenous adminstration MR Scan: Standard of Care
Period Title: Overall Study
STARTED	21
Bone Sarcoma	10
Osteomyelitis	4
Lymphoma	7
COMPLETED	21
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Feraheme
Arm/Group Description	Intravenous injection of Feraheme, 5 mg Fe/kg Feraheme: 5 mg Fe/kg by intravenous adminstration MR Scan: Standard of Care
Overall Participants	21
Age (Count of Participants)
<=18 years	16 76.2%
Between 18 and 65 years	5 23.8%
>=65 years	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	14.7 (4.0)
Sex: Female, Male (Count of Participants)
Female	11 52.4%
Male	10 47.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 19%
Not Hispanic or Latino	16 76.2%
Unknown or Not Reported	1 4.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 4.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	19 90.5%
More than one race	0 0%
Unknown or Not Reported	1 4.8%
Region of Enrollment (participants) [Number]
United States	21 100%

Outcome Measures

1. Primary Outcome

Title	T2* Relaxation Time of Bone Sarcomas and Osteomyelitis Subjects
Description	Differentiation of bone sarcomas and osteomyelitis with ferumoxytol-enhanced magnetic resonance imaging (MRI) was assessed as the difference of mean T2 * relaxation time of bone sarcoma and osteomyelitis subjects. The outcome is reported as the difference of the mean T2 * values, with standard deviation.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

This initial phase of the study was a pilot assessment of participants with bone sarcomas compared to participants with osteomyelitis.

Arm/Group Title	Bone Sarcomas	Osteomyelitis
Arm/Group Description	Participants with bone sarcomas (osteosarcomas and Ewing sarcomas) evaluated with ferumoxytol-enhanced MRI.	Participants with osteomyelitis evaluated with MRI with ferumoxytol enhancement.
Measure Participants	5	4
Mean (Standard Deviation) [milliseconds]	7.3 (1.9)	7.7 (1.9)

2. Secondary Outcome

Title	Differentiation of Bone Sarcomas Pre-ferumoxytol and Post-ferumoxytol Contrast
Description	Differentiation of bone sarcomas pre-ferumoxytol and post-ferumoxytol contrast was assessed by difference of mean T2 * relaxation time pre-ferumoxytol and post-ferumoxytol contrast, in bone sarcoma subjects only.
Time Frame	Baseline and Post-Treatment-24 hours

Outcome Measure Data

Analysis Population Description

Only the participants with bone sarcomas were evaluated for this outcome.

Arm/Group Title	Bone Sarcomas Pre-ferumoxytol & Post-ferumoxytol Contrast
Arm/Group Description	Participants with bone sarcomas (osteosarcomas and Ewing sarcomas) only.
Measure Participants	10
Pre-treatment	13.80 (2.80)
Post-treatment	8.27 (2.12)

3. Secondary Outcome

Title	Differentiation of Lymphoma and Bone Sarcomas With Ferumoxytol-enhanced MRI
Description	Differentiation of lymphoma from bone sarcoma was assessed as the difference of mean T2 * relaxation time determined by ferumoxytol-enhanced MRI. .
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

The analysis population for this outcome includes the participants with bone sarcoma who participated in the pilot study.

Arm/Group Title	Mean T2 * Relaxation Time for Lymphoma Participants	Mean T2 * Relaxation Time for Bone Sarcoma Participants
Arm/Group Description	Participants with lymphoma evaluated with ferumoxytol-enhanced MRI	Participants with bone sarcoma, evaluated with ferumoxytol-enhanced MRI
Measure Participants	7	10
Mean (Standard Deviation) [milliseconds]	14.83 (1.03)	7.71 (0.60)

4. Secondary Outcome

Title	Differentiation of CD68-positive Tumor-associated Macrophages (TAM) in Lymphomas and Bone Sarcomas
Description	Differentiation of CD68-positive tumor-associated macrophages (TAM) between lymphoma and bone sarcoma was assessed as the difference of mean area density of CD68-positive TAM in those populations.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mean Area Density of CD-68-positive TAM in Lymphoma	Mean Area Density of CD-68-positive TAM in Bone Sarcomas
Arm/Group Description	CD-68-positive tumor-associated macrophages (TAM) assessed in Lymphoma participants	CD-68-positive Tumor associated macrophages(TAMs)in Bone Sarcomas participants
Measure Participants	7	10
Mean (Standard Deviation) [Percentage of CD68-positive TAM]	4.8 (1.2)	6.1 (2.3)

5. Secondary Outcome

Title	Differentiation of CD163-positive Tumor-associated Macrophages (TAM) in Lymphomas and Bone Sarcomas
Description	Differentiation of CD163-positive tumor-associated macrophages (TAM) between lymphoma and bone sarcoma was assessed as the difference of mean area density of CD163-positive TAM in those populations.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mean Area Density of CD163-positive TAM in Lymphoma	Mean Area Density of CD163-positive TAM in Bone Sarcoma
Arm/Group Description	CD163-positive tumor-associated macrophages (TAM) was assessed in participants with lymphoma	CD163-positive tumor-associated macrophages (TAM) was assessed in participants with bone sarcomas
Measure Participants	7	10
Mean (Standard Deviation) [Percentage area of CD163-positive TAM]	1.9 (1.5)	9.4 (3.1)

Adverse Events

Time Frame	24 hours
Arm/Group Title	Feraheme
Arm/Group Description	Intravenous injection of Feraheme, 5 mg Fe/kg Feraheme: 5 mg Fe/kg iv MR Scan: Standard of Care
All Cause Mortality
	Feraheme
	Affected / at Risk (%)	# Events
Total	0/21 (0%)
Serious Adverse Events
	Feraheme
	Affected / at Risk (%)	# Events
Total	0/21 (0%)
Other (Not Including Serious) Adverse Events
	Feraheme
	Affected / at Risk (%)	# Events
Total	1/21 (4.8%)
Immune system disorders
Allergic reaction	1/21 (4.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.