| Eligibility |
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.
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