Primary Liver CancerPhase 4NCT03215355
Improving CBCT for Liver IG-SBRT Using Gadoxetate Disodium
A Phase 4 study testing Primovist in people with Primary Liver Cancer and Metastatic Liver Cancer, run by Slawa Cwajna at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Liver Cancer, Metastatic Liver Cancer
- What is being tested?
- Primovist
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2017to Aug 2018
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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
Who cannot join
- 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)
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Improving Cone-beam Computed Tomography for Image Guided Stereotactic Body Radiation Therapy of the Liver Using Gadoxetate Disodium
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.
Read the 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.
- Conditions
- Primary Liver Cancer, Metastatic Liver Cancer
- Being tested
- Primovist
- Keywords
- Adaptive radiotherapy, Contrast media, Cone-beam computed tomography, Stereotactic body radiation therapy
- Medical subject headings
- Carcinoma, Hepatocellular, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrimovistDrug
Also called Gadoxetate disodium, Gd-EoB-DTPA
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Primovist |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (1)
Toxicity with "off label" dosing
Categorized as adverse reaction or no adverse reaction post monitoring.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2017
- Study startAug 2017 (estimated)
- Primary completionAug 2018 (estimated)
- Study completionAug 2018 (estimated)
Why it stopped: Not approved
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Liver CancerStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Slawa Cwajna
- Sponsor type
- University, hospital or other
- Collaborators
- Nova Scotia Health Authority
- Responsible party
- Sponsor-investigator, Slawa Cwajna, Nova Scotia Health Authority
- Investigators
- Slawa Cwajna, MD, Principal investigator, Nova Scotia Health Authority
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03215355
- Sponsor's protocol ID
- NSHAREB#4793
- Status last verified
- Jan 2021
- First submitted
- 5 Jul 2017
- Last updated
- 27 Jan 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Cone-beam Computed Tomography for Image Guided Stereotactic Body Radiation Therapy of the Liver Using Gadoxetate Disodium
- ClinicalTrials.gov ID
- NCT03215355
- Acronym / sponsor ID
- NSHAREB#4793
- Conditions
- Primary Liver Cancer, Metastatic Liver Cancer
- Keywords
- Adaptive radiotherapy, Contrast media, Cone-beam computed tomography, Stereotactic body radiation therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Not approved
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Slawa CwajnaUniversity, hospital or other
- Collaborators
- Nova Scotia Health Authority
- Study start
- Aug 2017 (estimated)
- Primary completion
- Aug 2018 (estimated)
- Study completion
- Aug 2018 (estimated)
- First posted
- 12 Jul 2017 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants receiving Primovist | Experimental | Drug: PrimovistBecause 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (13 listed)
- 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
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 |
|---|---|---|
| PrimovistAlso: Gadoxetate disodium, Gd-EoB-DTPAPrimovist 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. | Drug | Participants receiving Primovist |
Primary outcome
Improved image quality after injection as determined by contrast-to-background calculation and expert observation.
Time frame: 12 months
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.
1 secondary outcome
Toxicity with "off label" dosing
Time frame: 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2021.
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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.
Slawa Cwajna, MD principal investigator
Nova Scotia Health Authority
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Primovist in people with Primary Liver Cancer and Metastatic Liver Cancer, run by Slawa Cwajna at 1 site in Canada.
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 12 inclusion and 13 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: withdrawn, as of the sponsor's last update on 27 Jan 2021. 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 Canada. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Improved image quality after injection as determined by contrast-to-background calculation and expert observation. (time frame: 12 months). 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 27 Jan 2021.