Liver NeoplasmsNCT04682847
Radiotherapy With Iron Oxide Nanoparticles (SPION) on MR-Linac for Primary & Metastatic Hepatic Cancers
An observational study of Liver Neoplasms and Hepatic Cirrhosis, run by Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute) at 1 site in United States.
Trial summary
There is a high prevalence of hepatic cirrhosis in patients with hepatocellular carcinomas (HCC), or chemotherapy-induced hepatic atrophy or hepatosteatosis in patients with liver metastases associated with high risk of radiation-induced liver disease (RILD) after stereotactic body radiotherapy (SBRT). Read more about this study
- Who is it for?
- Ages 18 to 89 years
- Conditions the study is for
- Liver Neoplasms, Hepatic Cirrhosis, Hepatic Carcinoma
- What is being tested?
- Ferumoxytol injection
- Type of treatment
- Injection or infusion
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Nov 2020to 31 Dec 2024
- Phase
- Observational
- 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 18 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with primary and metastatic liver tumors and hepatic cirrhosis eligible for liver SBRT will be enrolled in this study who will be receiving treatment at Allegheny General Hospital, Pittsburgh, PA.
Who may be able to join
- Patients age 18-89 years
- Women of childbearing age must have a negative urine/serum pregnancy test (per standard of care) and must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study Women beyond childbearing are not required to use contraception.
- Child-Pugh A or B liver function;
- Child-Pugh C liver function for transplant eligible patients only.
- Single or multinodular tumors (up to four) are permitted.
- Patients required to have more than 30% of functionally active uninvolved liver outside radiation target volume;
- No prior liver radiation, including radioembolization;
- ECOG (Eastern Cooperative Oncology Group) performance score >=2
Who cannot join
- Patients over 90 year of age
- Bilirubin x3 upper limit of normal;
- AST (aspartate aminotransferase) or ALT (alanine transaminase) x6 upper limit of normal;
- Hemoglobin less than 80 g/L;
- Patients with recurrent ascites (paracentesis q ≥2 weeks);
- Patients with history of hypersensitivity to Feraheme or any other IV iron products;
- Patients with hemochromatosis (iron overload).
Trial locations and contacts
1 site in 1 country.
United States1 site
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
About this study
Official title: Adaptive Stereotactic Radiotherapy With Superparamagnetic Iron Oxide Nanoparticles (SPION) Cellular Magnetic Resonance Imaging on MR-Linac (MR-L-SPION) for Primary and Metastatic Hepatic Malignancies With Assessment of Treatment Response.
There is a high prevalence of hepatic cirrhosis in patients with hepatocellular carcinomas (HCC), or chemotherapy-induced hepatic atrophy or hepatosteatosis in patients with liver metastases associated with high risk of radiation-induced liver disease (RILD) after stereotactic body radiotherapy (SBRT). MRI-SPION radiotherapy planning will facilitate detection and maximize avoidance of residual functionally active hepatic parenchyma from over-the-threshold irradiation thus increasing safety of liver SBRT in patients with pre-existing liver conditions. The investigators have previously demonstrated that liver SBRT with SPECT/CT functional treatment planning utilizing 99mTc sulfur colloid in transplant eligible patients associated with minimal hepatotoxicity and without hastening of advanced hepatic cirrhosis progression while patients await liver transplant. Switching from nuclear medicine to an MR-Linac-SPION based quantitative treatment-planning platform will substantially improve diagnostic accuracy in defining safe volumes of residual functional hepatic parenchyma for liver SBRT planning on MR-Linac.
Read the detailed description
Setting/Participants:
The study will be performed at a single center - Allegheny General Hospital (AGH) in a setting of referral-based outpatients within the Allegheny Health (AHN) network.
25 patients with primary and metastatic liver tumors and hepatic cirrhosis eligible for liver SBRT will be enrolled in this study.
Study Interventions and Measures:
MRI cellular imaging of hepatic parenchyma with SPION will be performed on a 1.5T MRI (Elekta MR-Linac) on the day of radiotherapy planning. Hepatic SPION accumulation will be quantified and delineated to designate volumes for conformal avoidance on the MR-Linac during liver SBRT. This quantitative assessment will be compared to the already established methodology using CT/SPECT images developed at AGH. Treatment outcomes and toxicity due to improved conformal avoidance of functional normal liver volumes will be assessed for these patients. Dose-response of tumor and hepatic parenchyma to SBRT will be examined using MR-Linac imaging, pathologic criteria and molecular profiling of explanted livers in a subset of patients who received liver SBRT as a bridge to transplant.
Main outcome of the study:
Development and evaluation of a novel MRI-Linac based functional treatment planning platform with DICOM-compatible applications for visualization and subsequent conformal avoidance of residual, functionally active hepatic parenchyma in patients undergoing liver SBRT to primary and metastatic malignancies with the assessment of tumor and hepatic parenchyma response using MR imaging correlated with both pathologic and genomic criteria in a subset of patients receiving SBRT as a bridge to liver transplant.
- Conditions
- Liver Neoplasms, Hepatic Cirrhosis, Hepatic Carcinoma, Liver Cancer, Liver Metastases, Liver Carcinoma
- Being tested
- Ferumoxytol injection
- Keywords
- Liver, Liver Cancer, Liver Carcinoma, Liver Metastases
- Medical subject headings
- Liver Neoplasms, Liver Cirrhosis, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ferumoxytol injectionDrug
Also called Feraheme™ (ferumoxytol) Injection
This is a prospective observation study of 1.5T MR-Linac-SPION imaging with Ferumoxytol for radiotherapy planning in patients with pre-existing liver condition in order to increase safety of liver SBRT with assessment of tumor and hepatic parenchyma response.
| Study group | Role | What they receive |
|---|---|---|
| Primary and metastatic liver tumors and hepatic cirrhosis | This study is a single arm prospective study that will enroll 25 patients with primary and metastatic liver tumors and hepatic cirrhosis eligible for liver SBRT who will be receiving treatment at a single center - Allegheny General Hospital. Receives: Drug: Ferumoxytol injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Develop a platform to maintain liver functionality during treatment for liver cancer
The primary goal of the study is to develop MRI-linac SPION based radiotherapy planning platform for detection and conformal avoidance of residual, functionally active hepatic parenchyma during liver SBRT for primary and metastatic hepatic malignancies in patients with hepatic cirrhosis. Treatment outcomes and toxicity due to improved conformal avoidance of functional normal liver volumes will be assessed for these patients.
Progression in Child-Pugh and MELD scores, disease free survival, and overall survival (with and without liver transplant) will be evaluated via Kaplan Meier analysis. Freedom from MELD score progression will be measured against residual volumes of functionally active hepatic parenchyma defined on MRI-linac SPION via Cox proportional hazard regression models. Statistical analysis will be conducted with MedCalc version 11.3.
Measured: Two Years
Secondary outcomes (2)
Develop applications for assessing the liver functionality of those with liver cancer
MRI and planning CT images will be co-registered using deformable image registration, and volumes with SPIO accumulation will be delineated as avoidance structures by the physician and clinical physicist. DICOM-compatible applications will be developed for contouring and quantitative assessment of functionally active volumes of hepatic parenchyma obtained from MR-Linac-SPIO images with subsequent conformal avoidance in the beam placement process during 3-D Conformal radiotherapy planning.
A non-contrast enhanced liver MR images will be acquired per fraction with propagation of the previously identified avoidance volumes in the adapted plans.
Follow-up MR-imaging of the patients will be obtained to assess tumor and hepatic parenchyma response treatment.
Measured: Two Years
Examine the dose-response of tumor and liver tissue in patients who received liver transplant after receiving SBRT
The dose-response of tumor and hepatic parenchyma to SBRT will be examined using MR imaging (on MR-Linac), pathologic criteria and molecular profiling of explanted livers in a subset of patients who received liver SBRT as a bridge to transplant.
In patients undergoing liver transplant MRI data sets will be merged with 3D dosimetry data and evaluated by a clinical physicist. Radiographic liver responses will be compared with explant liver pathology. The pathologic and genomic analysis will document both tumor and hepatic parenchymal response to SBRT. The chronology of tumor and hepatic parenchymal response and regeneration to radiotherapy will be evaluated. Initial 3D dosimetry will be combined with the pathologic assessment to determine any dose threshold for healthy liver regeneration following SBRT with MR-Linac SPION functional imaging.
Measured: Two Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2020
- Study start19 Nov 2020
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver NeoplasmsStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alexander Kirichenko, Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
- Investigators
- Alexander Kirichenko, MD, PhD, Principal investigator, Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04682847
- Sponsor's protocol ID
- 2020-212
- Status last verified
- Jan 2024
- First submitted
- 24 Nov 2020
- Last updated
- 31 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Only de-identified data will be shared with collaborators of the trial.
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adaptive Stereotactic Radiotherapy With Superparamagnetic Iron Oxide Nanoparticles (SPION) Cellular Magnetic Resonance Imaging on MR-Linac (MR-L-SPION) for Primary and Metastatic Hepatic Malignancies With Assessment of Treatment Response.
- ClinicalTrials.gov ID
- NCT04682847
- Acronym / sponsor ID
- 2020-212
- Conditions
- Liver Neoplasms, Hepatic Cirrhosis, Hepatic Carcinoma, Liver Cancer, Liver Metastases, Liver Carcinoma
- Keywords
- Liver, Liver Cancer, Liver Carcinoma, Liver Metastases
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)University, hospital or other
- Study start
- 19 Nov 2020 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 24 Dec 2020 (actual)
- 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.
There is a high prevalence of hepatic cirrhosis in patients with hepatocellular carcinomas (HCC), or chemotherapy-induced hepatic atrophy or hepatosteatosis in patients with liver metastases associated with high risk of radiation-induced liver disease (RILD) after stereotactic body radiotherapy (SBRT). MRI-SPION radiotherapy planning will facilitate detection and maximize avoidance of residual functionally active hepatic parenchyma from over-the-threshold irradiation thus increasing safety of liver SBRT in patients with pre-existing liver conditions. The investigators have previously demonstrated that liver SBRT with SPECT/CT functional treatment planning utilizing 99mTc sulfur colloid in transplant eligible patients associated with minimal hepatotoxicity and without hastening of advanced hepatic cirrhosis progression while patients await liver transplant. Switching from nuclear medicine to an MR-Linac-SPION based quantitative treatment-planning platform will substantially improve diagnostic accuracy in defining safe volumes of residual functional hepatic parenchyma for liver SBRT planning on MR-Linac.
Detailed description
Setting/Participants:
The study will be performed at a single center - Allegheny General Hospital (AGH) in a setting of referral-based outpatients within the Allegheny Health (AHN) network.
25 patients with primary and metastatic liver tumors and hepatic cirrhosis eligible for liver SBRT will be enrolled in this study.
Study Interventions and Measures:
MRI cellular imaging of hepatic parenchyma with SPION will be performed on a 1.5T MRI (Elekta MR-Linac) on the day of radiotherapy planning. Hepatic SPION accumulation will be quantified and delineated to designate volumes for conformal avoidance on the MR-Linac during liver SBRT. This quantitative assessment will be compared to the already established methodology using CT/SPECT images developed at AGH. Treatment outcomes and toxicity due to improved conformal avoidance of functional normal liver volumes will be assessed for these patients. Dose-response of tumor and hepatic parenchyma to SBRT will be examined using MR-Linac imaging, pathologic criteria and molecular profiling of explanted livers in a subset of patients who received liver SBRT as a bridge to transplant.
Main outcome of the study:
Development and evaluation of a novel MRI-Linac based functional treatment planning platform with DICOM-compatible applications for visualization and subsequent conformal avoidance of residual, functionally active hepatic parenchyma in patients undergoing liver SBRT to primary and metastatic malignancies with the assessment of tumor and hepatic parenchyma response using MR imaging correlated with both pathologic and genomic criteria in a subset of patients receiving SBRT as a bridge to liver transplant.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Primary and metastatic liver tumors and hepatic cirrhosis | – | Drug: Ferumoxytol injectionThis study is a single arm prospective study that will enroll 25 patients with primary and metastatic liver tumors and hepatic cirrhosis eligible for liver SBRT who will be receiving treatment at a single center - Allegheny General Hospital. |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with primary and metastatic liver tumors and hepatic cirrhosis eligible for liver SBRT will be enrolled in this study who will be receiving treatment at Allegheny General Hospital, Pittsburgh, PA.
Key inclusion criteria (8 listed)
- Patients age 18-89 years
- Women of childbearing age must have a negative urine/serum pregnancy test (per standard of care) and must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study Women beyond childbearing are not required to use contraception.
- Child-Pugh A or B liver function;
- Child-Pugh C liver function for transplant eligible patients only.
- Single or multinodular tumors (up to four) are permitted.
Key exclusion criteria (7 listed)
- Patients over 90 year of age
- Bilirubin x3 upper limit of normal;
- AST (aspartate aminotransferase) or ALT (alanine transaminase) x6 upper limit of normal;
- Hemoglobin less than 80 g/L;
- Patients with recurrent ascites (paracentesis q ≥2 weeks);
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 |
|---|---|---|
| Ferumoxytol injectionAlso: Feraheme™ (ferumoxytol) InjectionThis is a prospective observation study of 1.5T MR-Linac-SPION imaging with Ferumoxytol for radiotherapy planning in patients with pre-existing liver condition in order to increase safety of liver SBRT with assessment of tumor and hepatic parenchyma response. | Drug | Primary and metastatic liver tumors and hepatic cirrhosis |
Primary outcome
Develop a platform to maintain liver functionality during treatment for liver cancer
Time frame: Two Years
The primary goal of the study is to develop MRI-linac SPION based radiotherapy planning platform for detection and conformal avoidance of residual, functionally active hepatic parenchyma during liver SBRT for primary and metastatic hepatic malignancies in patients with hepatic cirrhosis. Treatment outcomes and toxicity due to improved conformal avoidance of functional normal liver volumes will be assessed for these patients. Progression in Child-Pugh and MELD scores, disease free survival, and overall survival (with and without liver transplant) will be evaluated via Kaplan Meier analysis. Freedom from MELD score progression will be measured against residual volumes of functionally active hepatic parenchyma defined on MRI-linac SPION via Cox proportional hazard regression models. Statistical analysis will be conducted with MedCalc version 11.3.
2 secondary outcomes
Develop applications for assessing the liver functionality of those with liver cancer
Time frame: Two Years
Examine the dose-response of tumor and liver tissue in patients who received liver transplant after receiving SBRT
Time frame: Two Years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2024.
- Individual participant dataSharing planned: No. Only de-identified data will be shared with collaborators of the trial.
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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.
Alexander Kirichenko, MD, PhD principal investigator
Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Neoplasms and Hepatic Cirrhosis, run by Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute) 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 8 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 31 Jan 2024. 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?
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?
Develop a platform to maintain liver functionality during treatment for liver cancer (time frame: Two Years). 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 31 Jan 2024.