Hepatocellular CarcinomaNCT01850316
Hepatocellular Carcinoma Using Stereotactic Body Radiotherapy
A study testing Stereotactic Ablative Radiotherapy in people with Hepatocellular Carcinoma, run by British Columbia Cancer Agency at 1 site in Canada.
Trial summary
Respiratory-gated, volumetric-modulated arc therapy will be used for the clinical development of high dose rate Stereotactic Body Radiotherapy (SBRT) in inoperable hepatocellular carcinoma (HCC). These treatments should enhance local control, progression-free survival and potentially overall survival in HCC patients. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Stereotactic Ablative Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2013to Aug 2020
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age > 18 years old
- Multi-phase CT scan of the liver within 8 weeks of radiation planning demonstrating:
- Liver tumours must be > 5 cm
- No more than 5 discrete liver tumours may be present
- Normal liver > 700 cc
- FDG-PET scan within 12 weeks prior to radiation planning
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)
- Liver HCC must be deemed unresectable as determined by an experienced liver surgeon, or the patient must be medically inoperable or refuse surgery, and extra-hepatic metastases must not be present (Patients with potential resectable tumours who are deemed unresectable based on medical inoperability or simultaneous extra-hepatic metastases will be eligible to receive SBRT).
- Patients must be discussed in a multidisciplinary setting where opinions regarding radiofrequency ablation, various embolotherapies, and targeted biologics are considered, but not eligible for. Patients must have recovered from the effects of previous therapies before SBRT.
- Eastern Clinical Oncology Group performance status 0,1 or 2 or a Karnofsky performance status of ≥ 60
- 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 2x upper limit of normal
- Child-Turcotte-Pugh assessment (within 8 weeks of treatment date):
- 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 (see Table 1 in Section 2.1)
- BCLC Stage B or C (portal venous invasion or liver hilum nodal disease only)
- No extra-hepatic disease and life expectancy > 6 months
- No chemotherapy concurrent with radiotherapy
- Previous treatment(s) with radiofrequency ablation, surgery, TACE, Y90, percutaneous ethanol injection, or chemotherapy are not exclusion criteria provided that recurrence has been documented.
- 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
1 site in 1 country.
About this study
Official title: A Phase II Study for the Treatment of Unresectable or Medically Inoperable Hepatocellular Carcinoma Using Stereotactic Body Radiotherapy (SBRT) in British Columbia
Respiratory-gated, volumetric-modulated arc therapy will be used for the clinical development of high dose rate Stereotactic Body Radiotherapy (SBRT) in inoperable hepatocellular carcinoma (HCC). These treatments should enhance local control, progression-free survival and potentially overall survival in HCC patients. The investigators will also examine the mechanism of tumour and microenvironmental response to high dose radiation, and search for potential biomarkers to optimize and individualize therapy. Pre-treatment and follow-up PET/CT imaging with 11C-choline, 18F-fluorodeoxyglucose (FDG) and CT perfusion will examine in-vivo changes in proliferation, glycolysis, and the tumour vasculature, respectively, and blood samples will look for immunologic biomarkers of tumour response.
Read the detailed description
Radiotherapy is not considered standard of care practice for patients for inoperable hepatocellular carcinoma despite the tumour's inherent radiosensitivity. The major challenge has been improving radiation delivery without exceeding dose limits of the surrounding normal liver. Recent technological advances with tumour localization and targeting, imaging, treatment planning and delivery have allowed for safe delivery of radiation with tumorcidal effect and minimal treatment-related toxicity.
This study has three specific aims:
- To develop, validate, and quality test HDR Stereotactic Body Radiotherapy (SBRT) Gated RapidArc technique for application in human liver tumours. And furthermore, to test whether HDR SBRT Gated RapidArc can be efficiently and safely delivered to a very large patient population previously ineligible for any therapy (HCC patients with tumours >5cm).
- To determine if 11C-choline/18F-FDG CT-PET or perfusion CT imaging (that characterize changes in tumour proliferation, glycolysis, and vasculature, respectively) can provide practical non-invasive biomarkers of tumour response, local tumour control, or normal tissue toxicity.
- To determine if immunologic studies of pre- and post-treatment blood samples can provide biomarkers of tumour response, local and systemic tumour control, or triggers for normal tissue toxicity.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Stereotactic Ablative Radiotherapy
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic Ablative RadiotherapyRadiation
Preferred target coverage of 40 Gy: coverage and total dose determined by irradiated liver volume NTCP (normal tissue complication probability) nomogram and OAR dose limits
| Study group | Role | What they receive |
|---|---|---|
| Stereotactic Ablative Radiotherapy | Experimental | Preferred target coverage of 40 Gy: coverage and total dose determined by irradiated liver volume NTCP (normal tissue complication probability) nomogram and OAR dose limits Receives: Radiation: Stereotactic Ablative Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
One year local progression-free rate
Measured: Approximately 1 year
Secondary outcomes (6)
Progression-free survival
Measured: To be reviewed in approximately 8 years; upon study completion
Overall Survival
Measured: To be reviewed in approximately 8 years; upon study completion
Treatment related toxicity
Measured: To be reviewed in approximately 8 years; upon study completion
Quality of Life
Measured: To be reviewed in approximately 8 years; upon study completion
Cytokine response to radiation and association with complications
Measured: To be reviewed in approximately 8 years; upon study completion
Functional imaging with 11C-choline/18F-FDG CT-PET and perfusion CT to that characterize treatment-related effects
Measured: To be reviewed in approximately 8 years; upon study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2013 (estimated)
- Study startJul 2013
- Primary completionAug 2018 (estimated)
- Study completionAug 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by British Columbia Cancer AgencyThe sponsor's other registered studies.
- 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
- Health services research
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- British Columbia Cancer Agency
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Roy Ma, MD, Principal investigator, British Columbia Cancer Agency
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01850316
- Sponsor's protocol ID
- H13-00481
- Status last verified
- Jan 2018
- First submitted
- 7 May 2013
- Last updated
- 18 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study for the Treatment of Unresectable or Medically Inoperable Hepatocellular Carcinoma Using Stereotactic Body Radiotherapy (SBRT) in British Columbia
- ClinicalTrials.gov ID
- NCT01850316
- Acronym / sponsor ID
- H13-00481
- Conditions
- Hepatocellular Carcinoma
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 13 participants (actual)
- Lead sponsor
- British Columbia Cancer AgencyUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Aug 2018 (estimated)
- Study completion
- Aug 2020 (estimated)
- First posted
- 9 May 2013 (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.
Respiratory-gated, volumetric-modulated arc therapy will be used for the clinical development of high dose rate Stereotactic Body Radiotherapy (SBRT) in inoperable hepatocellular carcinoma (HCC). These treatments should enhance local control, progression-free survival and potentially overall survival in HCC patients. The investigators will also examine the mechanism of tumour and microenvironmental response to high dose radiation, and search for potential biomarkers to optimize and individualize therapy. Pre-treatment and follow-up PET/CT imaging with 11C-choline, 18F-fluorodeoxyglucose (FDG) and CT perfusion will examine in-vivo changes in proliferation, glycolysis, and the tumour vasculature, respectively, and blood samples will look for immunologic biomarkers of tumour response.
Detailed description
Radiotherapy is not considered standard of care practice for patients for inoperable hepatocellular carcinoma despite the tumour's inherent radiosensitivity. The major challenge has been improving radiation delivery without exceeding dose limits of the surrounding normal liver. Recent technological advances with tumour localization and targeting, imaging, treatment planning and delivery have allowed for safe delivery of radiation with tumorcidal effect and minimal treatment-related toxicity.
This study has three specific aims:
- To develop, validate, and quality test HDR Stereotactic Body Radiotherapy (SBRT) Gated RapidArc technique for application in human liver tumours. And furthermore, to test whether HDR SBRT Gated RapidArc can be efficiently and safely delivered to a very large patient population previously ineligible for any therapy (HCC patients with tumours >5cm).
- To determine if 11C-choline/18F-FDG CT-PET or perfusion CT imaging (that characterize changes in tumour proliferation, glycolysis, and vasculature, respectively) can provide practical non-invasive biomarkers of tumour response, local tumour control, or normal tissue toxicity.
- To determine if immunologic studies of pre- and post-treatment blood samples can provide biomarkers of tumour response, local and systemic tumour control, or triggers for normal tissue toxicity.
Study design
- Primary purpose
- Health services research
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Stereotactic Ablative Radiotherapy | Experimental | Radiation: Stereotactic Ablative RadiotherapyPreferred target coverage of 40 Gy: coverage and total dose determined by irradiated liver volume NTCP (normal tissue complication probability) nomogram and OAR dose limits |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Age > 18 years old
- Multi-phase CT scan of the liver within 8 weeks of radiation planning demonstrating:
- FDG-PET scan within 12 weeks prior to radiation planning
- 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)
- Liver HCC must be deemed unresectable as determined by an experienced liver surgeon, or the patient must be medically inoperable or refuse surgery, and extra-hepatic metastases must not be present (Patients with potential resectable tumours who are deemed unresectable based on medical inoperability or simultaneous extra-hepatic metastases will be eligible to receive 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 |
|---|---|---|
| Stereotactic Ablative RadiotherapyPreferred target coverage of 40 Gy: coverage and total dose determined by irradiated liver volume NTCP (normal tissue complication probability) nomogram and OAR dose limits | Radiation | Stereotactic Ablative Radiotherapy |
Primary outcome
One year local progression-free rate
Time frame: Approximately 1 year
6 secondary outcomes
Progression-free survival
Time frame: To be reviewed in approximately 8 years; upon study completion
Overall Survival
Time frame: To be reviewed in approximately 8 years; upon study completion
Treatment related toxicity
Time frame: To be reviewed in approximately 8 years; upon study completion
Quality of Life
Time frame: To be reviewed in approximately 8 years; upon study completion
Cytokine response to radiation and association with complications
Time frame: To be reviewed in approximately 8 years; upon study completion
Functional imaging with 11C-choline/18F-FDG CT-PET and perfusion CT to that characterize treatment-related effects
Time frame: To be reviewed in approximately 8 years; upon study completion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2018.
Related trials for Hepatocellular Carcinoma
RecruitingPhase 1/2
A Phase 1 and 2 Study of VMD-102 in Hepatocellular Carcinoma and Other Solid Tumors
Hepatocellular Carcinoma (HCC), Metastatic Uveal Melanoma
Not yet recruitingPhase 2
Study Evaluating the Efficacy and Safety of BGB-B2033 in Participants With Advanced Hepatocellular Carcinoma
Hepatocellular Cancer, Liver Cancer
Active, not recruitingPhase 1/2
Nivolumab, Fluorouracil, and Interferon Alpha 2B for the Treatment of Unresectable Fibrolamellar Cancer
Stage III Hepatocellular Carcinoma AJCC v8, Stage IIIA Hepatocellular Carcinoma AJCC v8
Not yet recruitingObservational study
Integration of Imaging, Molecular, Pathological, and Clinical Outcome Data in Hepatocellular Carcinoma.
Resectable Hepatocellular Carcinoma (HCC)
Active, not recruitingPhase 3
Radiation Therapy With Protons or Photons in Treating Patients With Liver Cancer
Recurrent Hepatocellular Carcinoma, Stage III Hepatocellular Carcinoma AJCC v7
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.
Roy Ma, MD principal investigator
British Columbia Cancer Agency
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stereotactic Ablative Radiotherapy in people with Hepatocellular Carcinoma, run by British Columbia Cancer Agency 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 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 18 Jan 2018. 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.
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?
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?
One year local progression-free rate (time frame: Approximately 1 year). 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 18 Jan 2018.