Clinical trial NCT04682847: Radiotherapy With Iron Oxide Nanoparticles (SPION) on MR-Linac for Primary & Metastatic Hepatic Cancers
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.
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Liver Neoplasms
Hepatic Cirrhosis
Hepatic Carcinoma
Liver Cancer
Liver Metastases
Liver Carcinoma
Hepatocellular Carcinoma
Hepatocellular Cancer
Hepatic Atrophy
Keywords: Liver
Liver Cancer
Liver Carcinoma
Liver Metastases
Lead sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
Sponsor class: OTHER
First posted: 2020-12-24
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
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.

Brief 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). 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.

Eligibility criteria: Inclusion Criteria:

1. Patients age 18-89 years
2. 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.
3. Child-Pugh A or B liver function;
4. Child-Pugh C liver function for transplant eligible patients only.
5. Single or multinodular tumors (up to four) are permitted.
6. Patients required to have more than 30% of functionally active uninvolved liver outside radiation target volume;
7. No prior liver radiation, including radioembolization;
8. ECOG (Eastern Cooperative Oncology Group) performance score \>=2

Exclusion Criteria:

1. Patients over 90 year of age
2. Bilirubin x3 upper limit of normal;
3. AST (aspartate aminotransferase) or ALT (alanine transaminase) x6 upper limit of normal;
4. Hemoglobin less than 80 g/L;
5. Patients with recurrent ascites (paracentesis q ≥2 weeks);
6. Patients with history of hypersensitivity to Feraheme or any other IV iron products;
7. Patients with hemochromatosis (iron overload).

Primary outcomes:
measure: Develop a platform to maintain liver functionality during treatment for liver cancer
timeFrame: Two Years
Secondary outcomes:
measure: Develop applications for assessing the liver functionality of those with liver cancer
timeFrame: Two Years
measure: Examine the dose-response of tumor and liver tissue in patients who received liver transplant after receiving SBRT
timeFrame: Two Years
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
Study officials:
affiliation: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
name: Alexander Kirichenko, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: