Molecular-Functional Imaging of Hypoxia in Childhood Sarcomas

Study Overview
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Brief Summary
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This study will test the feasibility of using novel/existing imaging technologies focused on hypoxia measurements to determine response to therapy in pediatric soft tissue sarcomas as a pilot study. Specifically, the investigators will compare the sensitivity of Blood Oxygen Level Dependent [BOLD], Diffusion-Weighted [DW] MRI, Magnetic Resonance Spectroscopy (MRS) and 18F-FAZA PET-MRI with that of conventional MRI to detect measurement changes between the start and completion of neoadjuvant therapy (response to therapy) in children and adolescents (7-18 years) with suspicion of sarcoma tumors. Clinicians and scientists may use results of the proposed hypoxia-imaging surrogate markers to adjust/modify therapeutic schemes to patients on a personalized basis.

Official Title
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Molecular-Functional Imaging of Hypoxia in Childhood Sarcomas: Feasibility Steps Toward Personalized Medicine.

Conditions
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Rhabdomyosarcoma, Non-Rhabdo. Soft Tissue Sarcoma

Intervention / Treatment
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* Drug: 18F-FAZA (F18-Fluoroazomycin Arabinoside)
* Diagnostic Test: Blood Oxygen Level Dependent [BOLD] MRI
* Diagnostic Test: Diffusion-Weighted [DW] MRI
* Diagnostic Test: Magnetic Resonance Spectroscopy [MRS]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Referred with a confirmed or suspected sarcoma tumor (rhabdomyosarcoma [RMS] or non-rhabdomyomatous sarcoma) presenting with an extra-osseous component; Candidate for neoadjuvant therapy that will consist of standard systemic chemotherapy with or without radiation therapy Exclusion Criteria: Patients with general contraindications for an MRI scan (metal foreign body, pacemaker, inability to tolerate an examination without sedation); Patients with a known immunodeficiency/sickle cell disease/collagen vascular disease/another malignancy; Patients with no clinical indication for neoadjuvant therapy prior to surgery; Patients with chronic pulmonary disease; Patients with other diagnosis confirmed after initial suspicion of RMS or non-RMS.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FAZA - BOLD- DW- MRS<br>18F-FAZA (F18-Fluoroazomycin Arabinoside) is a radioactive agent developed as a non-invasive probe for the assessment of cellular hypoxia. 18F-FAZA Injection is indicated in a single dose of (5.2 MBq/kg [0.14 mCi/kg]) Route/method of administration: intravenous injection. Blood Oxygen Level Dependent [BOLD], Diffusion-Weighted [DW] MRI, MR Spectroscopy [MRS] | Drug: 18F-FAZA (F18-Fluoroazomycin Arabinoside)<br>* Intravenous administration of a hypoxia marker, 18F- Fluoroazomycin arabinoside (FAZA), before a PET-MR imaging in order to identify areas of lower oxygen content on samples of a tumour.<br>* Other names: 18F- FAZA;Diagnostic Test: Blood Oxygen Level Dependent [BOLD] MRI<br>* BOLD is a non-invasive T2*-weighted MRI technique that is sensitive to the microvascular deoxyhemoglobin concentration. BOLD has the potential to monitor changes in tissue oxygenation in response to a gas breathing challenge to induce contrast.<br>Diagnostic Test: Diffusion-Weighted [DW] MRI<br>* DW MRI is a non-invasive technique that provides quantitative biophysical information about the movement of water in tissues and reflects the anisotropy of normal and pathologic cells<br>Diagnostic Test: Magnetic Resonance Spectroscopy [MRS]<br>* MRS is a non-invasive imaging technique that enables the generation of spectral profiles of low molecular weight metabolites that reflect status of a tissue<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with response to therapy | Response will be assessed by measurements of tumor volume, percentage of BOLD signal changes, percentage of tumor necrosis, apparent diffusion coefficient, concentration of high-energy and low-energy phosphates in tumor and necrotic areas and 18F-FAZA uptake. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Associations between post-neoadjuvant therapy imaging measurements and surgical / histochemical outcomes in the residual tumor. |  | 1 year |