Clinical trial NCT03215355: Improving CBCT for Liver IG-SBRT Using Gadoxetate Disodium
Official title: Improving Cone-beam Computed Tomography for Image Guided Stereotactic Body Radiation Therapy of the Liver Using Gadoxetate Disodium
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Primary Liver Cancer
Metastatic Liver Cancer
Keywords: Adaptive radiotherapy
Contrast media
Cone-beam computed tomography
Stereotactic body radiation therapy
Lead sponsor: Nova Scotia Health Authority
Sponsor class: OTHER
Collaborators: name: Nova Scotia Health Authority
First posted: 2017-07-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: Preliminary testing has already been performed and proves the notion that to achieve adequate image quality in a CT imaging phantom, at least 4 times the MRI administration dose would be required. These conclusions were supported qualitatively by a radiologist, radiation oncologist, and medical physicist, while also being backed up by quantitative measurement that has been accepted in the medical imaging literature. It is important for this work to first ensure that the imaging system is optimized, to have confidence that it will be successful for patients. Therefore before this study begins, substantial time and effort will be spent using phantoms and optimizing the imaging parameters and protocol.

The current procedure for a patient that presents with liver cancer begins with a referral from the patient's primary care physician for stereotactic body radiation therapy (SBRT). A radiation oncologist makes the decision whether the patient is suitable for SBRT.

If the patient is deemed acceptable by the radiation oncologist, the next step is to undergo diagnostic imaging so that the radiation oncologist can identify where exactly the disease is located, and start the SBRT plan. Using the diagnostic images, the radiation oncologist outlines the areas to treat, as well as the areas that they want to spare. This information is given to a physicist who then plans the optimal way of delivering radiation based on the oncologist's specifications. Once the plan is approved by the radiation oncologist, the patient can be treated.

At the time of treatment, the patient is placed in an immobilization device on a treatment couch by a radiation therapist. Once the patient is immobilized, an x-ray imaging system that is attached to the treatment machine extends out towards the patient. The machine performs a 180-degree rotation with continuous x-ray imaging. Once sufficient imaging has been performed, the therapists then align these images with the previous diagnostic CT image that was used to plan the radiation treatment. This alignment process tells the radiation therapists how much to adjust the patient on the treatment couch to ensure the most accurate treatment delivery. Once the patient is in the proper position, the radiation treatment is delivered and then the patient can leave.

The treatment procedure is then performed on five separate days each separated by 48 hours.

The proposed research follows the same procedure with addition of a contrast injection at the treatment stage. A consent form will be given to the patient entailing the purpose of this study. It will highlight the risks and benefits of receiving contrast prior to the radiation treatment, as well as a complete outline of the research. If the patient consents to receiving an intravenous contrast injection of gadoxetate disodium then the treatment procedure will change as follows:

Before the patient is placed in the immobilization device, a MRI technologist with experience giving gadoxetate disodium injections will give the prescribed injection according to the patient's body weight. After the injection is given, a liver SBRT trained radiation therapist will lead the patient to the treatment machine and set them up in the immobilization device as per standard treatments. The same time-of-treatment imaging will be performed, with the hypothesis that the image quality will improve because of the addition of the contrast agent. The contrast agent will only be administered at the first treatment because of the limited data on repeat injections of the drug in humans. Furthermore, for the first treatment when contrast is administered, a radiation oncologist, radiologist, medical physicist, MRI technologist, and three radiation therapists will attend.

The patient will then be monitored for another 30 minutes with support equipment ready in the rare event that a side effect occurs.

As per standard treatments, the radiation oncologist will follow up with patients at regular intervals during and after treatment, making sure to check with the patient for possible side effects of using the contrast agent.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Improved image quality after injection as determined by contrast-to-background calculation and expert observation.
timeFrame: 12 months
Secondary outcomes:
measure: Toxicity with "off label" dosing
timeFrame: 12 months
Other outcomes:
Locations:
city: Halifax
country: Canada
facility: Nova Scotia Cancer Centre
state: Nova Scotia
Study officials:
affiliation: Nova Scotia Health Authority
name: Slawa Cwajna, MD
role: PRINCIPAL_INVESTIGATOR
References: