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Quantitative Imaging Biomarkers of Treatment Response in Osteosarcoma and Ewing Sarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01882231
Recruitment Status : Terminated (Slow accrual and lack of funding)
First Posted : June 20, 2013
Last Update Posted : May 8, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Vicki Keedy, MD, Vanderbilt-Ingram Cancer Center

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.

Condition or disease Intervention/treatment Phase
Osteosarcoma Paget's Disease Ewing Sarcoma Other: DCE-MRI, DW-MRI, MT-MRI, and CEST-MRI Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Quantitative Imaging Biomarkers of Treatment Response in Osteosarcoma and Ewing Sarcoma
Study Start Date : March 2013
Actual Primary Completion Date : April 25, 2016
Actual Study Completion Date : April 25, 2016

Arm Intervention/treatment
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.
Imaging techniques using high-field MRI to make quantitative assessments in patients with osteosarcoma or Ewing sarcoma
Other 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

Primary Outcome Measures :
  1. Percent change in MRI metrics [ Time Frame: Pre-treatment and end of neoadjuvant cycle 1 ]
    Use 3T CEST-MRI, DW-MRI, and DCE-MRI to quantitatively measure protein content (APTasym), tumor cellularity (ADC), and tumor perfusion (Ktrans)and measure changes in these parameters from baseline to post 1 cycle of neoadjuvant chemotherapy.

Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: From first dose of neo-adjuvant chemotherapy to disease progression, date of last follow-up, or death ]
    Duration from first dose of neo-adjuvant chemotherapy to disease progression, date of last follow-up, or death for any reason

  2. Percent of tumor necrosed at surgical resection [ Time Frame: At surgical resection, post-cycle 3 of neoadjuvant chemotherapy, or post-cycle 2 if tumor has progressed. ]
    Percent of necrosis in the excised tumor specimen determined by the reading pathologist.

  3. Percent change in tumor size [ Time Frame: Pre-treatment and at the end of cycle 2 of neoadjuvant chemotherapy ]
    Standard of care imaging, either CT or MRI, will be performed prior to the initiation of neoadjuvant chemotherapy and at the end of cycle 2 using standard RECIST 1.1 guidelines summarized as follows for target lesion criteria (see RECIST v1.1 for additional details): complete response (CR),disappearance of target lesions; partial response (PR), >=30% decrease in sum of longest diameter of target lesions; progressive disease (PD), >=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or SD. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR>PR>SD>PD.

Information from the National Library of Medicine

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Ages Eligible for Study:   13 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01882231

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United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
National Cancer Institute (NCI)
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Principal Investigator: Vicki Keedy, MD Vanderbilt-Ingram Cancer Study
Additional Information:
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Responsible Party: Vicki Keedy, MD, Assistant Professor of Medicine; Clinical Director, Sarcoma Program; Medical Director, Clinical Trials Shared Resource; Medical Oncologist, Vanderbilt-Ingram Cancer Center Identifier: NCT01882231    
Other Study ID Numbers: VICC SAR 1275
U01CA142565 ( U.S. NIH Grant/Contract )
First Posted: June 20, 2013    Key Record Dates
Last Update Posted: May 8, 2017
Last Verified: May 2017
Keywords provided by Vicki Keedy, MD, Vanderbilt-Ingram Cancer Center:
Ewing sarcoma
Paget's disease
bone cancer
childhood cancers
Additional relevant MeSH terms:
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Sarcoma, Ewing
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue