Quantitative Imaging Biomarkers of Treatment Response in Osteosarcoma and Ewing Sarcoma
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.
Other: DCE-MRI, DW-MRI, MT-MRI, and CEST-MRI
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||Quantitative Imaging Biomarkers of Treatment Response in Osteosarcoma and Ewing Sarcoma|
- Percent change in MRI metrics [ Time Frame: Pre-treatment and end of neoadjuvant cycle 1 ] [ Designated as safety issue: No ]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.
- Progression-free survival [ Time Frame: From first dose of neo-adjuvant chemotherapy to disease progression, date of last follow-up, or death ] [ Designated as safety issue: No ]Duration from first dose of neo-adjuvant chemotherapy to disease progression, date of last follow-up, or death for any reason
- 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. ] [ Designated as safety issue: No ]Percent of necrosis in the excised tumor specimen determined by the reading pathologist.
- Percent change in tumor size [ Time Frame: Pre-treatment and at the end of cycle 2 of neoadjuvant chemotherapy ] [ Designated as safety issue: No ]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.
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||February 2017 (Final data collection date for primary outcome measure)|
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.
Other: 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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01882231
|Contact: VICC Clinical Trials Information Program||800-811-8480|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center||Recruiting|
|Nashville, Tennessee, United States, 37232|
|Contact: VICC Clinical Trials Information Program|
|Principal Investigator: Vicki Keedy, MD|
|Principal Investigator:||Vicki Keedy, MD||Vanderbilt-Ingram Cancer Study|