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Quantitative Imaging Biomarkers of Treatment Response in Osteosarcoma and Ewing Sarcoma

Primary Purpose

Osteosarcoma, Paget's Disease, Ewing Sarcoma

Status

Terminated

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

DCE-MRI, DW-MRI, MT-MRI, and CEST-MRI

About this trial

This is an interventional diagnostic trial for Osteosarcoma focused on measuring Osteosarcoma, Ewing sarcoma, Paget's disease, bone cancer, childhood cancers, DCE MRI, DW MRI, CEST MRI, MT MRI

Eligibility Criteria

13 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Vanderbilt-Ingram Cancer Center

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

DCE-MRI, DW-MRI, MT-MRI, and CEST-MRI

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Progression-free survival

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

Percent of necrosis in the excised tumor specimen determined by the reading pathologist.

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.

Full Information

NCT ID

NCT01882231

First Posted

May 29, 2013

Last Updated

May 3, 2017

Sponsor

Vanderbilt-Ingram Cancer Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01882231

Brief Title

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

2. Study Status

Record Verification Date

May 2017

Overall Recruitment Status

Terminated

Why Stopped

Slow accrual and lack of funding

Study Start Date

March 2013 (undefined)

Primary Completion Date

April 25, 2016 (Actual)

Study Completion Date

April 25, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Vanderbilt-Ingram Cancer Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

DCE-MRI, DW-MRI, MT-MRI, and CEST-MRI

Arm Type

Other

Arm Description

Intervention Type

Other

Intervention Name(s)

DCE-MRI, DW-MRI, MT-MRI, and CEST-MRI

Other Intervention Name(s)

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

Intervention Description

Imaging techniques using high-field MRI to make quantitative assessments in patients with osteosarcoma or Ewing sarcoma

Primary Outcome Measure Information:

Title

Percent change in MRI metrics

Description

Time Frame

Pre-treatment and end of neoadjuvant cycle 1

Secondary Outcome Measure Information:

Title

Progression-free survival

Description

Duration from first dose of neo-adjuvant chemotherapy to disease progression, date of last follow-up, or death for any reason

Time Frame

From first dose of neo-adjuvant chemotherapy to disease progression, date of last follow-up, or death

Title

Percent of tumor necrosed at surgical resection

Description

Percent of necrosis in the excised tumor specimen determined by the reading pathologist.

Time Frame

At surgical resection, post-cycle 3 of neoadjuvant chemotherapy, or post-cycle 2 if tumor has progressed.

Title

Percent change in tumor size

Description

Time Frame

Pre-treatment and at the end of cycle 2 of neoadjuvant chemotherapy

10. Eligibility

Sex

All

Minimum Age & Unit of Time

13 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Vicki Keedy, MD

Organizational Affiliation

Vanderbilt-Ingram Cancer Study

Official's Role

Principal Investigator

Facility Information:

Facility Name

Vanderbilt-Ingram Cancer Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.vicc.org/ct/

Description

Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

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Quantitative Imaging Biomarkers of Treatment Response in Osteosarcoma and Ewing Sarcoma

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