Quantitative Imaging Biomarkers of Treatment Response in Osteosarcoma and Ewing Sarcoma

Osteosarcoma Clinical Trial

Official title:

Quantitative Imaging Biomarkers of Treatment Response in Osteosarcoma and Ewing Sarcoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01882231
• Other study ID #: VICC SAR 1275
• Secondary ID: U01CA142565
• Status: Terminated
• Phase: N/A
• First received: May 29, 2013
• Last updated: May 3, 2017
• Start date: March 2013
• Est. completion date: April 25, 2016

Study information

• Verified date: May 2017
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: April 25, 2016
• Est. primary completion date: April 25, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ewing Sarcoma
• Osteosarcoma
• Paget's Disease
• Sarcoma
• Sarcoma, Ewing

Intervention

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

Locations

Country	Name	City	State
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change in MRI metrics	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.	Pre-treatment and end of neoadjuvant cycle 1
Secondary	Progression-free survival	Duration from first dose of neo-adjuvant chemotherapy to disease progression, date of last follow-up, or death for any reason	From first dose of neo-adjuvant chemotherapy to disease progression, date of last follow-up, or death
Secondary	Percent of tumor necrosed at surgical resection	Percent of necrosis in the excised tumor specimen determined by the reading pathologist.	At surgical resection, post-cycle 3 of neoadjuvant chemotherapy, or post-cycle 2 if tumor has progressed.
Secondary	Percent change in tumor size	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.	Pre-treatment and at the end of cycle 2 of neoadjuvant chemotherapy

External Links

•   Vanderbilt-Ingram Cancer Center, Find a Clinical Trial