Clinical trial NCT01882231: Quantitative Imaging Biomarkers of Treatment Response in Osteosarcoma and Ewing Sarcoma
Official title: Quantitative Imaging Biomarkers of Treatment Response in Osteosarcoma and Ewing Sarcoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Osteosarcoma
Paget's Disease
Ewing Sarcoma
Keywords: Osteosarcoma
Ewing sarcoma
Paget's disease
bone cancer
childhood cancers
DCE MRI
DW MRI
CEST MRI
MT MRI
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-06-20
Enrollment: 6
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Percent change in MRI metrics
timeFrame: Pre-treatment and end of neoadjuvant cycle 1
Secondary outcomes:
measure: Progression-free survival
timeFrame: From first dose of neo-adjuvant chemotherapy to disease progression, date of last follow-up, or death
measure: Percent of tumor necrosed at surgical resection
timeFrame: At surgical resection, post-cycle 3 of neoadjuvant chemotherapy, or post-cycle 2 if tumor has progressed.
measure: Percent change in tumor size
timeFrame: Pre-treatment and at the end of cycle 2 of neoadjuvant chemotherapy
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Study
name: Vicki Keedy, MD
role: PRINCIPAL_INVESTIGATOR
References: