Carcinoma, HepatocellularNCT02847767
Dynamic Contrast Enhanced HCC SABR Liver Study
A study testing Perfusion Imaging in people with Carcinoma, Hepatocellular, run by British Columbia Cancer Agency at 2 sites in Canada.
Trial summary
The high dose per fraction (>10Gy/fraction) used in Stereotactic Ablative Body Radiotherapy (SABR) has been shown to be more effective at local tumor control than treatments employing more conventional dose fractions. The mechanisms for this are currently under debate. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- Perfusion Imaging
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesCanada
- Study dates
- Jul 2016to Oct 2018
- Phase
- Interventional
- 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
- All the following criteria must be met:
- Age > 18 years old
- Multi-phase CT scan and/or MRI of the liver within 8 weeks of radiation planning demonstrating:
- Liver tumours < 5 cm
- No more than 2 discrete liver tumours
- Normal liver > 700 cc
Show all 27Show fewer
- Patients must have HCC diagnosed by either: i) pathological confirmation, or ii) intrahepatic vascular enhancement of the lesion demonstrated by at least two imaging modalities, or iii) intrahepatic vascular enhancement of the lesion demonstrated by one imaging modality if AFP > 200 in the setting of liver cirrhosis or chronic hepatitis B without cirrhosis (EASL consensus guidelines [2])
- Liver HCC must be deemed unresectable as determined by an experienced hepatobiliary surgeon, or the patient must be medically inoperable or refuse surgery,
- Patients must be discussed in a multidisciplinary setting, with representatives from Medical Oncology, Radiation Oncology, Surgery, Interventional Radiology, and Hepatology. Patients must be considered ineligible for standard local treatments, including surgery, liver transplantation, radiofrequency ablation, and targeted biologics. Some subjects could be potential candidates for sorafenib but normally this treatment is not considered before all local treatment options have been considered, as the response rate to sorafenib is low (2% in the SHARP study). Patients might be candidates for sorafenib after progression on the study treatment or if they do not want to participate and in both cases they will be referred to a medical oncologist. Patients may have received prior TACE and had an incomplete response. Ineffective or incomplete TACE is defined as incomplete filling by lipiodol-doxorubicin mixture used by either angiography or CT ≥1 month after TACE or by increasing alpha-fetoprotein level. Patients must have recovered from the effects of previous therapies before SBRT with a minimum 4-week period between TACE and SBRT.
- Eastern Clinical Oncology Group performance status 0, 1, or 2 (Appendix III), or a Karnofsky performance status of ≥ 60 (Appendix IV)
- Adequate organ function as assessed by the following blood work:
- Hemoglobin ≥ 90 g/L
- Absolute neutrophil count ≥ 1.0 bil/L
- Platelets ≥ 50 bil/L
- AST and ALT not to exceed 3x upper limit of normal
- Child-Turcotte-Pugh assessment within 8 weeks of treatment date (Appendix II):
- Bilirubin ≤ 3 mg/dL (< 50 µmol/L)
- Albumin above 28 g/L
- INR < 1.7 and/or correctable with vitamin K (unless on anticoagulation therapy)
- No ascites or encephalopathy
- Child-Turcotte-Pugh score must be ≤ 7
- BCLC Stage B or C (portal venous invasion or liver hilum nodal disease only; (Appendix I)
- Life expectancy > 6 months
- No chemotherapy or systemic therapy concurrent with radiotherapy
- Previous treatment(s) with radiofrequency ablation, surgery, TACE, Y90, percutaneous ethanol injection, or chemotherapy are not exclusion criteria provided that recurrence or lack of tumour response has been documented. Patients who decline, or not eligible for, these treatments will also be considered eligible.
- Patient signs a study-specific informed consent form. If the patient's mental status precludes this, written informed consent may be given by the patient's legal representative. A translator will be provided if the patient has a language barrier.
- Treatment plans meet acceptable dose constraints and Liver Veff is ≤ 0.55
Who cannot join
- Patients with active hepatitis, encephalopathy, or ascites related to liver failure
- Female patients who are pregnant (verify with blood test if patient is pre-menopausal). Pre-menopausal patients may also not become pregnant during participation in this study.
- Prior external beam radiation to the upper abdomen
- Patients with distant metastases or extrahepatic nodal progression (patients with portal venous thrombosis and liver hilum nodal involvement remain eligible)
- Patients who have < 700 cc of normal liver.
- Child-Turcotte-Pugh scores > 7
- BCLC Stage A, C (N1 and/or M1), D
- Prior gastric, duodenal, or variceal bleed within the past 2 months
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
BC Cancer Agency Fraser Valley Centre
Surrey, British Columbia, V3V 1Z2
BC Cancer Agency Vancouver Centre
Vancouver, British Columbia, V5Z 4E6
About this study
Official title: Dynamic Contrast Enhanced Imaging of Patients Receiving SABR for Unresectable or Medically Inoperable Hepatocellular Carcinoma in BC
The high dose per fraction (>10Gy/fraction) used in Stereotactic Ablative Body Radiotherapy (SABR) has been shown to be more effective at local tumor control than treatments employing more conventional dose fractions. The mechanisms for this are currently under debate. One possible mechanism for this increased effectiveness is that high dose/fraction causes significant vascular damage to the tumor. This study hopes to measure vascular integrity pre and post SABR treatment using kinetic models obtained from dynamic contrast enhanced CT.
Read the detailed description
Purpose:
The purpose of this study is to determine if high dose per fraction SABR has an impact on the vasculature of both the tumor and of healthy liver tissue.
Hypothesis:
High dose / fraction in HCC patients with tumours < 5 cm will result in detectable changes to kinetic model parameters derived from dynamic contrast enhanced images.
Objectives:
Primary objective:
To quantify changes in tumor vascular support for patients receiving SABR.
Secondary objectives:
To investigate the correlation between PK derived model liver perfusion parameters and QoL metrics as measured by EORTC QLQ-C30 and FACT-Hep QoL assessments.
Research Methods:
Target population are patients receiving liver SABR for no more than 2 discrete liver tumors with a maximum dimension <5cm.
Perfusion CT Image Data Post Processing and Analysis. Patient motion will be corrected using deformable registration, fiducial tracking, and RPM breathing traces. Organ ROIs will be added to the perfusion image series by manually translating anatomical planning CT ROIs to the motion-corrected perfusion image series, or by algorithmically deforming planning ROIs. Portal vein and abdominal aorta ROIs will be demarcated.
Analysis will proceed via custom software we have built during related projects. Contrast enhancement time courses will be generated for key structures (i.e., abdominal aorta, portal vein, and gross liver tissues) and used to derive a variety of perfusion map images, such as liver perfusion, mean transit time, arterial fraction, and distribution volume. A distributed parameter model will be preferred for kinetic modeling. Supplementary non-parametric techniques will be used for other parameters of interest (e.g., IAUC, maximum slope).
Images acquired before and after treatment will be registered so that parameter maps can be compared on a per-patient basis. Changes in perfusion parameters will be characterized with special emphasis placed on regional structure and clustering effects. Pre and post parameter maps will be computed near individual-voxel level. Regions of interest (1) within or near tumour and (2) at a low-dose portion of liver will be defined. A distribution of parameters within each ROI will be used to generate estimates of the mean parameters and uncertainty. Estimates of mean parameters and whole distributions will be compared using standard statistical comparisons (t-test and Whitney respectively).
Quality of Life We will evaluate quality of life (QOL) in HCC patients treated with SBRT using EORTC QLQ-C30 and FACT-Hep QOL assessments at baseline, 3, 6, 9 and 12 months. Correlation between perfusion parameter changes and patient outcomes or QOL (second-order analysis) will be applied if statistically significant first-order parameter changes can be detected. Standard correlative measures such as the Pearson product-moment correlation measure will be used to assess statistical significance. As there is currently no data relating liver perfusion to toxicity or quality of life, this study will examine whether a change in liver perfusion is correlated with enhanced or reduced QOL.
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- Perfusion Imaging
- Keywords
- Liver Perfusion, Hepatocellular Carcinoma, Dynamic Contrast-Enhanced Computed Tomography
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Perfusion ImagingProcedure or surgery
IV contrast perfusion CT will be performed at baseline and at 1 week after completing treatment. Perfusion imaging is similar to a diagnostic CT except a smaller region is serially imaged post contrast injection with multiple data acquisitions and high temporal resolution
| Study group | Role | What they receive |
|---|---|---|
| Perfusion Imaging | Experimental | IV contrast perfusion CT will be performed at baseline and at 1 week after completing treatment. Perfusion imaging is similar to a diagnostic CT except a smaller region is serially imaged post contrast injection with multiple data acquisitions and high temporal resolution. Receives: Procedure: Perfusion Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in tumour vasculature as assessed by changes PL derived model parameters
To quantify changes in tumor vascular support for patients receiving SABR.
Measured: 1 week after cancer treatment
Secondary outcomes (1)
Association (correlation) between aggregate QOL scores and PK derived model parameters
To investigate the correlation between PK derived model liver perfusion parameters and QOL metrics as measured by EORTC QLQ-C30 and FACT-Hep QOL assessments.
Measured: 1 week after cancer treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2016 (estimated)
- Study startJul 2016
- Primary completionOct 2018 (estimated)
- Study completionOct 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, HepatocellularStudies 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- British Columbia Cancer Agency
- Sponsor type
- University, hospital or other
- Collaborators
- University of British Columbia
- Responsible party
- Principal investigator, Francois Benard, British Columbia Cancer Agency
- Investigators
- Francois Benard, MD, Principal investigator, British Columbia Cancer Agency
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02847767
- Sponsor's protocol ID
- H15-02341
- Status last verified
- Jul 2016
- First submitted
- 5 Jul 2016
- Last updated
- 28 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dynamic Contrast Enhanced Imaging of Patients Receiving SABR for Unresectable or Medically Inoperable Hepatocellular Carcinoma in BC
- ClinicalTrials.gov ID
- NCT02847767
- Acronym / sponsor ID
- H15-02341
- Conditions
- Carcinoma, Hepatocellular
- Keywords
- Liver Perfusion, Hepatocellular Carcinoma, Dynamic Contrast-Enhanced Computed Tomography
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- British Columbia Cancer AgencyUniversity, hospital or other
- Collaborators
- University of British Columbia
- Study start
- Jul 2016
- Primary completion
- Oct 2018 (estimated)
- Study completion
- Oct 2018 (estimated)
- First posted
- 28 Jul 2016 (estimated)
- 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.
The high dose per fraction (>10Gy/fraction) used in Stereotactic Ablative Body Radiotherapy (SABR) has been shown to be more effective at local tumor control than treatments employing more conventional dose fractions. The mechanisms for this are currently under debate. One possible mechanism for this increased effectiveness is that high dose/fraction causes significant vascular damage to the tumor. This study hopes to measure vascular integrity pre and post SABR treatment using kinetic models obtained from dynamic contrast enhanced CT.
Detailed description
Purpose:
The purpose of this study is to determine if high dose per fraction SABR has an impact on the vasculature of both the tumor and of healthy liver tissue.
Hypothesis:
High dose / fraction in HCC patients with tumours < 5 cm will result in detectable changes to kinetic model parameters derived from dynamic contrast enhanced images.
Objectives:
Primary objective:
To quantify changes in tumor vascular support for patients receiving SABR.
Secondary objectives:
To investigate the correlation between PK derived model liver perfusion parameters and QoL metrics as measured by EORTC QLQ-C30 and FACT-Hep QoL assessments.
Research Methods:
Target population are patients receiving liver SABR for no more than 2 discrete liver tumors with a maximum dimension <5cm.
Perfusion CT Image Data Post Processing and Analysis. Patient motion will be corrected using deformable registration, fiducial tracking, and RPM breathing traces. Organ ROIs will be added to the perfusion image series by manually translating anatomical planning CT ROIs to the motion-corrected perfusion image series, or by algorithmically deforming planning ROIs. Portal vein and abdominal aorta ROIs will be demarcated.
Analysis will proceed via custom software we have built during related projects. Contrast enhancement time courses will be generated for key structures (i.e., abdominal aorta, portal vein, and gross liver tissues) and used to derive a variety of perfusion map images, such as liver perfusion, mean transit time, arterial fraction, and distribution volume. A distributed parameter model will be preferred for kinetic modeling. Supplementary non-parametric techniques will be used for other parameters of interest (e.g., IAUC, maximum slope).
Images acquired before and after treatment will be registered so that parameter maps can be compared on a per-patient basis. Changes in perfusion parameters will be characterized with special emphasis placed on regional structure and clustering effects. Pre and post parameter maps will be computed near individual-voxel level. Regions of interest (1) within or near tumour and (2) at a low-dose portion of liver will be defined. A distribution of parameters within each ROI will be used to generate estimates of the mean parameters and uncertainty. Estimates of mean parameters and whole distributions will be compared using standard statistical comparisons (t-test and Whitney respectively).
Quality of Life We will evaluate quality of life (QOL) in HCC patients treated with SBRT using EORTC QLQ-C30 and FACT-Hep QOL assessments at baseline, 3, 6, 9 and 12 months. Correlation between perfusion parameter changes and patient outcomes or QOL (second-order analysis) will be applied if statistically significant first-order parameter changes can be detected. Standard correlative measures such as the Pearson product-moment correlation measure will be used to assess statistical significance. As there is currently no data relating liver perfusion to toxicity or quality of life, this study will examine whether a change in liver perfusion is correlated with enhanced or reduced QOL.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Perfusion Imaging | Experimental | Procedure: Perfusion ImagingIV contrast perfusion CT will be performed at baseline and at 1 week after completing treatment. Perfusion imaging is similar to a diagnostic CT except a smaller region is serially imaged post contrast injection with multiple data acquisitions and high temporal resolution. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Age > 18 years old
- Multi-phase CT scan and/or MRI of the liver within 8 weeks of radiation planning demonstrating:
- Patients must have HCC diagnosed by either: i) pathological confirmation, or ii) intrahepatic vascular enhancement of the lesion demonstrated by at least two imaging modalities, or iii) intrahepatic vascular enhancement of the lesion demonstrated by one imaging modality if AFP > 200 in the setting of liver cirrhosis or chronic hepatitis B without cirrhosis (EASL consensus guidelines [2])
- Liver HCC must be deemed unresectable as determined by an experienced hepatobiliary surgeon, or the patient must be medically inoperable or refuse surgery,
- Patients must be discussed in a multidisciplinary setting, with representatives from Medical Oncology, Radiation Oncology, Surgery, Interventional Radiology, and Hepatology. Patients must be considered ineligible for standard local treatments, including surgery, liver transplantation, radiofrequency ablation, and targeted biologics. Some subjects could be potential candidates for sorafenib but normally this treatment is not considered before all local treatment options have been considered, as the response rate to sorafenib is low (2% in the SHARP study). Patients might be candidates for sorafenib after progression on the study treatment or if they do not want to participate and in both cases they will be referred to a medical oncologist. Patients may have received prior TACE and had an incomplete response. Ineffective or incomplete TACE is defined as incomplete filling by lipiodol-doxorubicin mixture used by either angiography or CT ≥1 month after TACE or by increasing alpha-fetoprotein level. Patients must have recovered from the effects of previous therapies before SBRT with a minimum 4-week period between TACE and SBRT.
Key exclusion criteria (8 listed)
- Patients with active hepatitis, encephalopathy, or ascites related to liver failure
- Female patients who are pregnant (verify with blood test if patient is pre-menopausal). Pre-menopausal patients may also not become pregnant during participation in this study.
- Prior external beam radiation to the upper abdomen
- Patients with distant metastases or extrahepatic nodal progression (patients with portal venous thrombosis and liver hilum nodal involvement remain eligible)
- Patients who have < 700 cc of normal liver.
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 |
|---|---|---|
| Perfusion ImagingIV contrast perfusion CT will be performed at baseline and at 1 week after completing treatment. Perfusion imaging is similar to a diagnostic CT except a smaller region is serially imaged post contrast injection with multiple data acquisitions and high temporal resolution | Procedure or surgery | Perfusion Imaging |
Primary outcome
Changes in tumour vasculature as assessed by changes PL derived model parameters
Time frame: 1 week after cancer treatment
To quantify changes in tumor vascular support for patients receiving SABR.
1 secondary outcome
Association (correlation) between aggregate QOL scores and PK derived model parameters
Time frame: 1 week after cancer treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2016.
- Individual participant dataSharing planned: No
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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.
Francois Benard, MD principal investigator
British Columbia Cancer Agency
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Perfusion Imaging in people with Carcinoma, Hepatocellular, run by British Columbia Cancer Agency at 2 sites 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 27 inclusion and 8 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 28 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
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?
Contact Steven Thomas (604-877-6000 ext. 2024, sthomas-02@bccancer.bc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in tumour vasculature as assessed by changes PL derived model parameters (time frame: 1 week after cancer treatment). 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 28 Jul 2016.