OsteosarcomaNCT01882231
Quantitative Imaging Biomarkers of Treatment Response in Osteosarcoma and Ewing Sarcoma
A study testing DCE-MRI, DW-MRI, MT-MRI, and CEST-MRI in people with Osteosarcoma and Paget's Disease, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- Osteosarcoma, Paget's Disease, Ewing Sarcoma
- What is being tested?
- DCE-MRI, DW-MRI, MT-MRI, and CEST-MRI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2013to 25 Apr 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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).
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
About this study
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.
Read the 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.
- Conditions
- Osteosarcoma, Paget's Disease, Ewing Sarcoma
- Being tested
- DCE-MRI, DW-MRI, MT-MRI, and CEST-MRI
- Keywords
- Osteosarcoma, Ewing sarcoma, Paget's disease, bone cancer, childhood cancers, DCE MRI, DW MRI, CEST MRI, MT MRI
- Medical subject headings
- Osteosarcoma, Osteitis Deformans, Sarcoma, Ewing, Bone Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DCE-MRI, DW-MRI, MT-MRI, and CEST-MRIOther
Also called Multi-parametric MRI, 3 Tesla MRI, Dynamic Contrast-Enhanced (DCE) MRI, Diffusion-Weighted (DW) MRI
Imaging techniques using high-field MRI to make quantitative assessments in patients with osteosarcoma or Ewing sarcoma
| Study group | Role | What they receive |
|---|---|---|
| DCE-MRI, DW-MRI, MT-MRI, and CEST-MRI | Other | 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. Receives: Other: DCE-MRI, DW-MRI, MT-MRI, and CEST-MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Pre-treatment and end of neoadjuvant cycle 1
Secondary outcomes (3)
Progression-free survival
Duration from first dose of neo-adjuvant chemotherapy to disease progression, date of last follow-up, or death for any reason
Measured: From first dose of neo-adjuvant chemotherapy to disease progression, date of last follow-up, or death
Percent of tumor necrosed at surgical resection
Percent of necrosis in the excised tumor specimen determined by the reading pathologist.
Measured: At surgical resection, post-cycle 3 of neoadjuvant chemotherapy, or post-cycle 2 if tumor has progressed.
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.
Measured: Pre-treatment and at the end of cycle 2 of neoadjuvant chemotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2013 (estimated)
- Study startMar 2013
- Primary completion25 Apr 2016
- Study completion25 Apr 2016
Why it stopped: Slow accrual and lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteosarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Vicki Keedy, MD, Vanderbilt-Ingram Cancer Center
- Investigators
- Vicki Keedy, MD, Principal investigator, Vanderbilt-Ingram Cancer Study
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01882231
- Sponsor's protocol ID
- VICC SAR 1275
- Other IDs
- U01CA142565
- Status last verified
- May 2017
- First submitted
- 29 May 2013
- Last updated
- 8 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantitative Imaging Biomarkers of Treatment Response in Osteosarcoma and Ewing Sarcoma
- ClinicalTrials.gov ID
- NCT01882231
- Acronym / sponsor ID
- VICC SAR 1275
- Conditions
- Osteosarcoma, Paget's Disease, Ewing Sarcoma
- Keywords
- Osteosarcoma, Ewing sarcoma, Paget's disease, bone cancer, childhood cancers, DCE MRI, DW MRI, CEST MRI
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual and lack of funding
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2013
- Primary completion
- 25 Apr 2016 (actual)
- Study completion
- 25 Apr 2016 (actual)
- First posted
- 20 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DCE-MRI, DW-MRI, MT-MRI, and CEST-MRI | Other | Other: DCE-MRI, DW-MRI, MT-MRI, and CEST-MRIPatients 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. |
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (14 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DCE-MRI, DW-MRI, MT-MRI, and CEST-MRIAlso: Multi-parametric MRI, 3 Tesla MRI, Dynamic Contrast-Enhanced (DCE) MRI, Diffusion-Weighted (DW) MRIImaging techniques using high-field MRI to make quantitative assessments in patients with osteosarcoma or Ewing sarcoma | Other | DCE-MRI, DW-MRI, MT-MRI, and CEST-MRI |
Primary outcome
Percent change in MRI metrics
Time frame: Pre-treatment and end of neoadjuvant cycle 1
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.
3 secondary outcomes
Progression-free survival
Time frame: From first dose of neo-adjuvant chemotherapy to disease progression, date of last follow-up, or death
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.
Percent change in tumor size
Time frame: Pre-treatment and at the end of cycle 2 of neoadjuvant chemotherapy
Results and safety
The study was stopped early (reason given: Slow accrual and lack of funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2017.
- Vanderbilt-Ingram Cancer Center, Find a Clinical TrialLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vicki Keedy, MD principal investigator
Vanderbilt-Ingram Cancer Study
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing DCE-MRI, DW-MRI, MT-MRI, and CEST-MRI in people with Osteosarcoma and Paget's Disease, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Slow accrual and lack of funding). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent change in MRI metrics (time frame: Pre-treatment and end of neoadjuvant cycle 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2017.