Hepatocellular CarcinomaNCT02511522
Study of Palliative Radiotherapy for Symptomatic Hepatocellular Carcinoma and Liver Metastases
A study testing Palliative Radiation Therapy in people with Hepatocellular Carcinoma and Liver Metastases, run by Canadian Cancer Trials Group at 7 sites in Canada.
Trial summary
The purpose of this study is to see whether one dose of palliative radiation therapy directed to the liver in combination with standard BSC might help to reduce liver pain/discomfort due to cancer when compared to getting standard BSC alone. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma, Liver Metastases
- What is being tested?
- Palliative Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 7 sitesCanada
- Study dates
- 11 Dec 2015to 2 Oct 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- A diagnosis of cancer by at least one criterion listed below:
- Pathologically or cytologically proven carcinoma from primary site or site of metastases;
- Pathologically or cytologically proven HCC;
- HCC diagnosed by standard imaging criteria: arterial enhancement and delayed washout on multiphasic computerized tomography (CT) or magnetic resonance imaging (MRI) in the setting of cirrhosis or chronic hepatitis B or C without cirrhosis.
- Largest burden of cancer in the liver is confirmed with CT scan or MRI corresponding to the clinically painful area done within 120 days prior to randomization.
- Diffuse (infiltrative involving > 50% of the liver), multifocal (> 10 lesions) or locally advanced cancer (at least one lesion > 10cm, vascular invasion, or multiple lesions with at least one > 6cm) involving the liver.
Show all 37Show fewer
- In the investigator's opinion, patient is unsuitable for or refractory to standard local and regional therapies. For example:
- HCC unsuitable for resection, radiofrequency ablation (RFA), transarterial chemo embolization (TACE) or radical intent, ablative dose stereotactic body radiation therapy (SBRT);
- Colorectal carcinoma metastases unsuitable for resection, RFA or radical intent, ablative dose SBRT (e.g. SBRT, > 30 Gy in 5 fractions, may be an option for up to 3 metastases < 5cm each, or up to 5 metastases < 3 cm each).
- Unsuitable for, high risk for, or refractory to, standard systemic chemotherapy or targeted therapy (e.g. sorafenib).
- Patient reports moderate or severe pain/discomfort prior to the baseline evaluation and this pain is considered "stable" over a period of up to 7 days prior to randomization.
- Definition of moderate pain:
- Patient reports level of 4-6 (on a BPI scale from 0 to 10) pain or discomfort "at its worst in the past 24 hours", occurring in the right upper quadrant of the abdomen, the upper abdomen and/or referred to the right shoulder, attributable to liver cancer.
- Definition of severe pain:
- Patient reports level of 7-10 (on a BPI scale from 0 to 10) pain or discomfort "at its worst in the past 24 hours", occurring in the right upper quadrant of the abdomen, the upper abdomen and/or referred to the right shoulder, attributable to liver cancer.
- Definition of "stable" pain:
- Patient must show moderate or severe "stable" pain by reporting a score of 4 or greater (on 2 separate days within the 7 day period prior to randomization) with the difference of these scores being 0, 1, 2 or 3.
- Patient reports moderate or severe pain (i.e. pain score is 4 or higher). This baseline score must also be stable compared to the most recent pre-baseline pain score with the difference between these scores being 0, 1, 2, or 3.
- Blood work obtained within 14 days prior to randomization as follows:
- Hemoglobin > 70 g/L;
- Platelets > 25 x 10^9/L
- Absolute neutrophil count (ANC) > 1.0 x 10^9/L
- INR < 3;
- Bilirubin < 2.5 UNL (except for subjects with Gilbert's Disease who are eligible despite elevated serum bilirubin level)
- AST or ALT < 10 x ULN.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-3 within 14 days of Randomization (see Appendix II).
- Life expectancy of > 3 months.
- 18 years of age or older at the time of randomization.
- Patient is willing to complete the Pre-Baseline Pain/Discomfort Questionnaire and the Pain/Discomfort and Medication Questionnaire in English, French or other validated language (please contact the HE.1 Study Coordinator). The baseline assessment must be completed within required timelines prior to randomization. Unwillingness to complete the Pre-Baseline Pain/Discomfort Questionnaire and Pain/Discomfort and Medication Questionnaire will make the patient ineligible for the study.
- Patient is able (i.e. sufficiently fluent) and willing to complete the QoL questionnaires in English, French or other languages in which the FACT-Hep is available. The baseline assessment must be completed within required timelines prior to randomization.
- Inability (illiteracy in languages listed above, loss of sight, or other equivalent reason) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the QoL questionnaires will make the patient ineligible for QoL assessment.
- Patient is not pregnant, planning on becoming pregnant or planning on fathering a child in the next 90 days.
- Women/men of childbearing potential must have agreed to use a highly effective contraceptive method. A woman is considered to be of "childbearing potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation, or vasectomy/vasectomized partner. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures.
- Women of childbearing potential will have a pregnancy test to determine eligibility as part of the Pre-Study Evaluation; this may include an ultrasound to rule-out pregnancy if a false-positive is suspected. For example, when beta-human chorionic gonadotropin is high and partner is vasectomized, it may be associated with tumour production of hCG, as seen with some cancers. Patient will be considered eligible if an ultrasound is negative for pregnancy
- Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrolment in the trial to document their willingness to participate;
- Patients must be accessible for treatment and follow-up. Investigators must ensure the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
- In accordance with NCIC CTG policy, protocol treatment is to begin within 5 working days of patient randomization (earlier is preferred).
Who cannot join
- Prior radiotherapy to the upper abdomen that would result in substantial overlap of the irradiated volume (e.g. > 50% of liver receiving > 24 Gy in 2 Gy equivalent dose);
- Prior selective internal radiotherapy directed to the liver or hepatic arterial yttrium therapy, at any time.
- Cholangitis or acute bacterial infection requiring intravenous antibiotics within 28 days prior to study entry.
- Radiographic evidence of intrabiliary cancer within the common or main branches of the biliary system, < 4 months prior to randomization.
- Child-Pugh score greater than C10 (a score of C10 is allowed).
- Chemotherapy or TACE administered within the past 4 weeks.
- Targeted therapy (e.g. Sorafenib) received within the past 2 weeks.
- Plans for chemotherapy, targeted therapy or TACE in the next 4 weeks.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Canada7 sites
Royal Victoria Regional Health Centre
Barrie, Ontario, L4M 6M2
Kingston Health Sciences Centre
Kingston, Ontario, K7L 2V7
CHUM-Centre Hospitalier de l'Universite de Montreal
Montreal, Quebec, H2X 3E4
Ottawa Hospital Research Institute
Ottawa, Ontario, K1H 8L6
Dr. H. Bliss Murphy Cancer Centre
St. John's, Newfoundland and Labrador, A1B 3V6
University Health Network
Toronto, Ontario, M5G 2M9
Centre hospitalier regional de Trois-Rivieres
Trois-Rivières, Quebec, G8Z 3R9
About this study
Official title: Phase III Study of Palliative Radiotherapy for Symptomatic Hepatocellular Carcinoma and Liver Metastases
The purpose of this study is to see whether one dose of palliative radiation therapy directed to the liver in combination with standard BSC might help to reduce liver pain/discomfort due to cancer when compared to getting standard BSC alone.
Read the detailed description
The standard treatment for liver cancer pain or discomfort like yours is known as best supportive care (BSC) and includes pain-relieving medicines called analgesics. This type of treatment can help in some cases; however, some analgesics require a healthy liver to work properly. This means that there are many patients who have a hard time managing their liver cancer pain/discomfort with BSC alone.
Sometimes radiation therapy is given in the "palliative" setting meaning it is designed to treat the pain/discomfort and not necessarily to shrink or eliminate the tumour. Palliative radiation therapy is often given when patients have painful bone tumours, but is not yet widely used to treat liver pain/discomfort. Palliative radiation therapy is usually given in smaller amounts and less frequently than other kinds of radiation therapy.
- Conditions
- Hepatocellular Carcinoma, Liver Metastases
- Being tested
- Best Supportive Care, Palliative Radiation Therapy
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Best Supportive CareOther
Including analgesics, palliative care and/or pain specialist assessment as needed
Palliative Radiation TherapyRadiation
8 Gy in 1 fraction in whole liver or near whole liver. Including anti-emetic pre-medications
| Study group | Role | What they receive |
|---|---|---|
| Best Supportive Care | Active comparator | Patients will be randomized 1:1 to receive best supportive care alone Receives: Other: Best Supportive Care |
| Best Supportive Care + RT 8 Gy/1 | Experimental | Patients will be randomized 1:1 to receive best supportive care plus radiation therapy (8 Gy in 1 fraction), Receives: Other: Best Supportive Care; Radiation: Palliative Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Patients Achieving Significant Improvement of Liver Cancer Pain/Discomfort
- Proportion of patients achieving improvement of liver cancer pain/discomfort by ≥ 2 points in pain "intensity at worst " on Brief Pain Inventory (BPI) from baseline to day 30.
Measured: 30 days
Secondary outcomes (3)
Proportion of Patients Alive at Day 90.
Estimated by Kaplan-Meier method for overall survival defined as time from randomization to death from any cause.
Measured: 90 days
Proportion of Patients Achieving a 25% Reduction in Opioid Use at 30 Days (Employing Daily Morphine Equivalence Scale).
Measured: 30 days
Proportion of Patients Achieving Improvement of Liver Cancer Pain/Discomfort by ≥ 2 Points in Pain "Intensity at Worst " AND With no Increase in Opioid Use (Employing Daily Morphine Equivalence Scale) on BPI From Baseline to 30 Days.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2015 (estimated)
- Study start11 Dec 2015
- Primary completion26 Oct 2022
- Study completion2 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Canadian Cancer Trials GroupThe 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Canadian Cancer Trials Group
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Laura Ann Dawson, Study chair, Univ. Health Network-Princess Margaret Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02511522
- Sponsor's protocol ID
- HE1
- Status last verified
- Oct 2024
- First submitted
- 23 Jul 2015
- Last updated
- 23 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dawson LA, Ringash J, Fairchild A, Stos P, Dennis K, Mahmud A, Stuckless TL, Vincent F, Roberge D, Follwell M, Wong RKW, Jonker DJ, Knox JJ, Zimmermann C, Wong P, Barry AS, Gaudet M, Wong RKS, Purdie TG, Tu D, O'Callaghan CJ. Palliative radiotherapy versus best supportive care in patients with painful hepatic cancer (CCTG HE1): a multicentre, open-label, randomised, controlled, phase 3 study. Lancet Oncol. 2024 Oct;25(10):1337-1346. doi: 10.1016/S1470-2045(24)00438-8. Epub 2024 Sep 5.
PubMed 39245060
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Study of Palliative Radiotherapy for Symptomatic Hepatocellular Carcinoma and Liver Metastases
- ClinicalTrials.gov ID
- NCT02511522
- Acronym / sponsor ID
- HE1
- Conditions
- Hepatocellular Carcinoma, Liver Metastases
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Canadian Cancer Trials GroupResearch network
- Study start
- 11 Dec 2015 (actual)
- Primary completion
- 26 Oct 2022 (actual)
- Study completion
- 2 Oct 2024 (actual)
- First posted
- 30 Jul 2015 (estimated)
- Results
- Posted 23 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to see whether one dose of palliative radiation therapy directed to the liver in combination with standard BSC might help to reduce liver pain/discomfort due to cancer when compared to getting standard BSC alone.
Detailed description
The standard treatment for liver cancer pain or discomfort like yours is known as best supportive care (BSC) and includes pain-relieving medicines called analgesics. This type of treatment can help in some cases; however, some analgesics require a healthy liver to work properly. This means that there are many patients who have a hard time managing their liver cancer pain/discomfort with BSC alone.
Sometimes radiation therapy is given in the "palliative" setting meaning it is designed to treat the pain/discomfort and not necessarily to shrink or eliminate the tumour. Palliative radiation therapy is often given when patients have painful bone tumours, but is not yet widely used to treat liver pain/discomfort. Palliative radiation therapy is usually given in smaller amounts and less frequently than other kinds of radiation therapy.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Best Supportive Care | Active comparator | Other: Best Supportive CarePatients will be randomized 1:1 to receive best supportive care alone |
| Best Supportive Care + RT 8 Gy/1 | Experimental | Other: Best Supportive Care, Radiation: Palliative Radiation TherapyPatients will be randomized 1:1 to receive best supportive care plus radiation therapy (8 Gy in 1 fraction), |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (37 listed)
- A diagnosis of cancer by at least one criterion listed below:
- Largest burden of cancer in the liver is confirmed with CT scan or MRI corresponding to the clinically painful area done within 120 days prior to randomization.
- Diffuse (infiltrative involving > 50% of the liver), multifocal (> 10 lesions) or locally advanced cancer (at least one lesion > 10cm, vascular invasion, or multiple lesions with at least one > 6cm) involving the liver.
- In the investigator's opinion, patient is unsuitable for or refractory to standard local and regional therapies. For example:
- Unsuitable for, high risk for, or refractory to, standard systemic chemotherapy or targeted therapy (e.g. sorafenib).
Key exclusion criteria (8 listed)
- Prior radiotherapy to the upper abdomen that would result in substantial overlap of the irradiated volume (e.g. > 50% of liver receiving > 24 Gy in 2 Gy equivalent dose);
- Prior selective internal radiotherapy directed to the liver or hepatic arterial yttrium therapy, at any time.
- Cholangitis or acute bacterial infection requiring intravenous antibiotics within 28 days prior to study entry.
- Radiographic evidence of intrabiliary cancer within the common or main branches of the biliary system, < 4 months prior to randomization.
- Child-Pugh score greater than C10 (a score of C10 is allowed).
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 |
|---|---|---|
| Best Supportive CareIncluding analgesics, palliative care and/or pain specialist assessment as needed | Other | Best Supportive Care, Best Supportive Care + RT 8 Gy/1 |
| Palliative Radiation Therapy8 Gy in 1 fraction in whole liver or near whole liver. Including anti-emetic pre-medications | Radiation | Best Supportive Care + RT 8 Gy/1 |
Primary outcome
Proportion of Patients Achieving Significant Improvement of Liver Cancer Pain/Discomfort
Time frame: 30 days
• Proportion of patients achieving improvement of liver cancer pain/discomfort by ≥ 2 points in pain "intensity at worst " on Brief Pain Inventory (BPI) from baseline to day 30.
3 secondary outcomes
Proportion of Patients Alive at Day 90.
Time frame: 90 days
Proportion of Patients Achieving a 25% Reduction in Opioid Use at 30 Days (Employing Daily Morphine Equivalence Scale).
Time frame: 30 days
Proportion of Patients Achieving Improvement of Liver Cancer Pain/Discomfort by ≥ 2 Points in Pain "Intensity at Worst " AND With no Increase in Opioid Use (Employing Daily Morphine Equivalence Scale) on BPI From Baseline to 30 Days.
Time frame: 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 39245060Dawson LA, Ringash J, Fairchild A, Stos P, Dennis K, Mahmud A, Stuckless TL, Vincent F, Roberge D, Follwell M, Wong RKW, Jonker DJ, Knox JJ, Zimmermann C, Wong P, Barry AS, Gaudet M, Wong RKS, Purdie TG, Tu D, O'Callaghan CJ. Palliative radiotherapy versus best supportive care in patients with painful hepatic cancer (CCTG HE1): a multicentre, open-label, randomised, controlled, phase 3 study. Lancet Oncol. 2024 Oct;25(10):1337-1346. doi: 10.1016/S1470-2045(24)00438-8. Epub 2024 Sep 5.
- 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.
Laura Ann Dawson study chair
Univ. Health Network-Princess Margaret Hospital
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Palliative Radiation Therapy in people with Hepatocellular Carcinoma and Liver Metastases, run by Canadian Cancer Trials Group at 7 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 37 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: finished, as of the sponsor's last update on 23 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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?
Yes. Results are posted in the registry (first posted 23 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Proportion of Patients Achieving Significant Improvement of Liver Cancer Pain/Discomfort (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02511522, which also lists 1 linked publication.
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 23 Oct 2024.