Study of Palliative Radiotherapy for Symptomatic Hepatocellular Carcinoma and Liver Metastases
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.
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.
Inclusion Criteria:

 -  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.

 -  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).

 Exclusion Criteria:

 -  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.