Quantitative Imaging Biomarkers of Treatment Response in Osteosarcoma and Ewing Sarcoma

NCT ID: NCT01882231

Last Updated: 2017-05-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2016-04-25

Brief Summary

The objective of these studies is to use changes in 3 Tesla MRI measurements of tumor protein content, cell density, and microvessel perfusion, obtained before and after a single cycle of NAC, to predict eventual tumor response observed at the conclusion of NAC, within patients with osteosarcoma or Ewing Sarcoma.

Detailed Description

Neoadjuvant chemotherapy (NAC) for osteosarcoma (OS) and Ewing sarcoma (ES) is associated with significant immediate and long-term complications, particularly difficult to endure in adolescent patients. Tumor response is assessed only at resection, often after the patient has received months of potentially toxic and ineffective therapy. Surgical approaches in this setting are extensive and life changing, with amputations not uncommon. Poor response to NAC is the single most important prognostic indicator in localized OS/ES. Early identification of those patients unlikely to benefit from the prescribed regimen could have significant clinical implications and allow for earlier adjustments in the patient's therapy. In patients with OS/ES there remains a compelling yet unmet need for more advanced quantitative, noninvasive imaging methods that can be deployed early after the initiation of treatment and which are capable of longitudinally measuring quantitative changes in relevant physiological, metabolic and/or biophysical parameters that can serve as reliable surrogates, or even predictors, of long-term tumor response to intervention, including pathological response at surgery. In this pilot study we will use multi-parametric 3 Tesla (3T) MRI, deployed before and after the first cycle of NAC, to correlate early changes in imaging biomarkers with the patient's eventual histopathological response at surgical resection. We will measure treatment-induced changes in: 1) protein content, measured via the amide proton transfer asymmetry (APTasym) using chemical exchange saturation transfer (CEST) MRI); 2) tumor fibrosis, measured via the magnetization transfer ratio (MTR) using magnetization transfer (MT) MRI); 3) tumor cellularity, measured via the apparent diffusion coefficient (ADC) using diffusion-weighted MRI); and 4) tumor perfusion, measured via the volume transfer coefficient (Ktrans) using dynamic contrast-enhanced DCE-MRI. The relevance and future clinical impact of each of these imaging biomarkers (alone or in combination) in OS/ES is potentially very high.

Conditions

Osteosarcoma; Paget's Disease; Ewing Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

DCE-MRI, DW-MRI, MT-MRI, and CEST-MRI

Patients will have dynamic contrast-enhanced (DCE), diffusion-weighted (DW), magnetization transfer (MT), and chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) performed before and after 1 cycle of chemotherapy.

Group Type: OTHER

DCE-MRI, DW-MRI, MT-MRI, and CEST-MRI

Intervention Type: OTHER

Imaging techniques using high-field MRI to make quantitative assessments in patients with osteosarcoma or Ewing sarcoma

Interventions

DCE-MRI, DW-MRI, MT-MRI, and CEST-MRI

Imaging techniques using high-field MRI to make quantitative assessments in patients with osteosarcoma or Ewing sarcoma

Intervention Type: OTHER

Other Intervention Names

Multi-parametric MRI; 3 Tesla MRI; Dynamic Contrast-Enhanced (DCE) MRI; Diffusion-Weighted (DW) MRI; Magnetization Transfer (MT) MRI; Chemical Exchange Saturation Transfer (CEST) MRI

Eligibility Criteria

Inclusion Criteria

• Subjects must be 13 years of age or older.
• Subjects (or their parent or legal guardian) must have signed Internal Review Board (IRB)-approved assent/informed consent documentation.
• Subjects must have histologically proven osteogenic sarcoma, malignant fibrous histiocytoma (MFH), or Ewing sarcoma.
• Subjects must be planned for resection (this includes localized resectable disease or patients with metastatic disease with planned palliative resection) and scheduled to begin neoadjuvant chemotherapy

Exclusion Criteria

• Subjects who are under 13 years of age.
• Subjects who have any type of bioimplant activated by mechanical, electronic, or magnetic means (e.g., cochlear implants, pacemakers, neurostimulators, biostimulators, electronic infusion pumps, etc), because such devices may be displaced or malfunction.
• Subjects who have any type of ferromagnetic bioimplant that could potentially be displaced.
• Subjects who have cerebral aneurysm clips.
• Subjects who may have shrapnel imbedded in their bodies (such as from war wounds), metal workers and machinists (potential for metallic fragments in or near the eyes).
• Subjects with inadequate renal function (creatinine ≥1.5 times upper limit of normal) or acute or chronic renal insufficiency (estimated glomerular filtration rate <30 mL/min).
• Subjects who are pregnant or breast feeding, because the effects of high field MRI on fetuses are not yet known. Urine pregnancy test/or serum human chorionic gonadotropin (HCG) will also be performed on women of child bearing potential.
• Subjects who have exhibited past allergic or other adverse reactions in response to intravenous injection of Magnevist® (gadopentetate dimeglumine) or other gadolinium-containing contrast agents.
• Subjects who exhibit noticeable anxiety and/or claustrophobia or who exhibit severe vertigo when they are moved into the magnet bore.
• Subjects incapable of giving informed written consent, for the following reasons:
• Inability to adhere to the experimental protocols for any reason
• Inability to communicate with the research team
• Limited ability to give informed consent due to mental disability, altered mental status, confusion, or psychiatric disorders
• Prisoners or other individuals deemed to be susceptible to coercion

• Minimum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Vicki Keedy, MD

Assistant Professor of Medicine; Clinical Director, Sarcoma Program; Medical Director, Clinical Trials Shared Resource; Medical Oncologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Vicki Keedy, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt-Ingram Cancer Study

Locations

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

Related Links

http://www.vicc.org/ct/

Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

Other Identifiers

U01CA142565

Identifier Type: NIH

Identifier Source: secondary_id

View Link

VICC SAR 1275

Identifier Type: -

Identifier Source: org_study_id