Improving CBCT for Liver IG-SBRT Using Gadoxetate Disodium

NCT03215355 | Withdrawn Phase 4

• 1 other identifier: NSHAREB#4793
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a feasibility study requiring only three patients to serve as a proof of concept that gadoxetate disodium (a liver specific contrast agent) can be used to improve images taken just before liver SBRT treatments. The hypothesis of this research is that if gadoxetate disodium improves image quality at the time of treatment, then it can be used for image guided radiotherapy (IGRT). Image guidance is the procedure where the 3D CT image that is used to plan a radiotherapy treatment, is aligned to a 3D image taken just before treatment. The better the alignment, the more accurate the treatment, which is crucial for high dose treatments such as SBRT. This research is important for two main reasons. First, it is much less invasive than the standard of care which involves surgically implanting markers in the liver that can move over time. The benefit to harm ratio for surgery, compared to an injection, is much more dramatic. Furthermore, not all patients are surgical candidates, and therefore in those cases radiation oncologists must prescribed a larger area to treat to ensure that none of the cancerous region is missed. The drawback to this method is the irradiation of more normal tissue than necessary, which although deemed to have a greater benefit than harm, is not ideal. Secondly, this research has strong implications in the field of radiation oncology to move towards patient oriented radiotherapy treatments. If successful, radiation treatment to the liver could be performed in less treatments because of the confidence given to radiation oncologists of the cancer location; knowing exactly the healthy liver regions to avoid.

Conditions

Primary Liver Cancer; Metastatic Liver Cancer

Keywords

Adaptive radiotherapy; Contrast media; Cone-beam computed tomography; Stereotactic body radiation therapy

Outcome Measures

Primary Outcomes (1)

• Improved image quality after injection as determined by contrast-to-background calculation and expert observation.

  Images will be read by a radiologist and radiation oncologist to qualitatively assess whether or not image enhancement occurred. This will be compared to the quantitative standard of calculating the amount of contrast in the region that is to be enhanced, compared to the surrounding normal tissue (background). Adequate enhancement will be taken as contrast-to-background ratio greater than 1.

  12 months

Secondary Outcomes (1)

• Toxicity with "off label" dosing

  12 months

Study Arms (1)

Participants receiving Primovist

EXPERIMENTAL

Because this is a proof of concept study, only one arm will be considered which is the patients that receive the one time contrast injection prior to their first treatment. The intervention is that although this drug is approved, an off label dosing regiment is being used to improve a separate imaging modality than what it was approved for. Based on preliminary phantom experiments and toxicity results in the literature, four times the dose was deemed safe and required to use for CBCT.

Drug: Primovist

Interventions

Primovist DRUG

Primovist is currently a drug marketed for MRI. In this study it will be administered intravenously at 4 times what it is quoted for MRI to enhance the different imaging modality (CBCT) to improve the accuracy of liver SBRT. Although liver SBRT usually consists of 5 treatments, contrast will only be administered during the first treatment. Consulting Health Canada and Bayer HealthCare Canada (the drug manufacturer) deemed this use "off label dosing" which in Canada is at the discretion of the physician. Based on preliminary imaging testing, and a review of toxicity literature for this drug, the administration for this specific use was deemed appropriate to give adequate image quality, while simultaneously maintaining patient safety.

Also known as: Gadoxetate disodium, Gd-EoB-DTPA

Participants receiving Primovist

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years and over
• Not suitable for surgery or radio-frequency ablation (RFA).
• Histologic confirmation of cancer diagnosis and/or histologic confirmation of liver malignancy
• Meets criteria for oligometastasis (not more than 5 metastases in total, none larger than 5cm in diameter, no more than 3 in any one organ).
• Child-Pugh: A
• \> 700cc uninvolved liver
• No limitation on the actual size of the tumor providing organ at risk (OAR) dose constraints can be met
• ECOG performance status 0-2
• Acceptable kidney and liver function : (AST/ALT/GGT, alkaline phosphate, total bilirubin, albumin), normal serum creatinine or Creatinine clearance \> 60mL/min
• Life expectancy \> 6 months
• No chemotherapy within 4 weeks
• Recurrence at the site of prior liver resection

You may not qualify if:

• Age less than 18 years
• Previous diagnosis of chronic sever renal insufficiency
• Previous diagnosis of acute renal failure
• Previous diagnosis of acute kidney injury
• Patients with biliary obstruction
• Impaired liver enzymes (\>6x ULN)
• Platelets \< 50 000
• \< 700cc of normal liver
• Ongoing or planned chemotherapy
• Progressing extra-hepatic disease
• History of active hepatitis
• Significant comorbidities within previous 6 months (unstable angina, MI, ascites, coagulopathy)
• Prior radiotherapy to site/sites of progressive disease

Sponsors & Collaborators

• Slawa Cwajna: lead
• Nova Scotia Health Authority: collaborator

Study Sites (1)

Nova Scotia Cancer Centre

Halifax, Nova Scotia, B3H 1V8, Canada

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

gadolinium ethoxybenzyl DTPA

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Slawa Cwajna, MD

  Nova Scotia Health Authority

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Radiation Oncologist (MD)

Study Record Dates

• First Submitted: July 5, 2017
• First Posted: July 12, 2017
• Study Start: August 1, 2017
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: January 27, 2021

Record last verified: 2021-01

Locations

CA (1)