Inclusion Criteria:
- Patients must have a radiologically consistent (early enhancement and delayed
enhancement washout) or pathologically confirmed diagnosis of hepatocellular carcinoma
that is not eligible for curative resection, transplantation, or ablative therapies.
- Prior radiation, liver directed therapy (including bland, chemo- or radioembolization,
or ablation), or hepatic resection are permitted if ≥4 weeks from start of therapy.
Extra-hepatic palliative radiation is permitted if completed ≥2 weeks prior to first
dose of study therapy and the patient has recovered to ≤ grade 1 toxicity.
- Patients must have radiographically measurable disease (RECIST1.1) in at least one
site not previously treated or with progression after radiation or liver directed
therapy (including bland, chemo- or radio-embolization, or ablation) either within the
liver or in a metastatic site.
- Patients must have either progressed or deemed intolerant of first-line systemic
therapy. More than one line of systemic therapy is not permitted. The last dose should
be at least 2 weeks from first dose of study therapy. Prior treatment may not contain
cabozantinib.
- Recovery to ≤ grade 1 from toxicities related to any prior treatments, unless the AEs
were clinically non-significant and/or stable on supportive therapy
- Must have a Child-Pugh score of B7 or B8
- Must have an ECOG performance status of 0-1.
- Ability to understand and willingness to sign IRB-approved informed consent.
- Willing to provide archived tissue, if available, from a previous diagnostic biopsy.
- Must be able to tolerate CT and/or MRI with contrast.
- Adequate organ function obtained ≤ 2 weeks prior to enrollment.
Exclusion Criteria:
- Must not have uncontrolled ascites (requiring paracentesis within 3 months of
screening) or hepatic encephalopathy requiring hospitalization (within 6 months of
screening)
- Must not have prior history of organ transplantation.
- No known brain metastasis unless adequately treated with radiotherapy and/or surgery
and stable for at least 4 weeks before registration. Eligible subjects must have been
without corticosteroid treatment at the time of registration.
- Must not have undergone a major surgery (e.g., GI surgery, removal or biopsy of brain
metastasis) within 8 weeks before first dose of study treatment. Complete wound
healing from major surgery must have occurred 1 month before first dose and from minor
surgery (e.g., simple excision, tooth extraction) at least 10 days before first dose.
Subjects with clinically relevant ongoing complications from prior surgery are not
eligible.
- Must not have an active second malignancy other than non-melanoma skin cancer or
cervical carcinoma in situ. Patients with history of malignancy are eligible provided
primary treatment of that cancer was completed > 1 year prior to enrollment and the
patient is free of clinical or radiologic evidence of recurrent or progressive
malignancy.
- Must not have uncontrolled, significant intercurrent or recent illness including, but
not limited to the following conditions:
- Cardiovascular disorders (Congestive heart failure or uncontrolled hypertension;
or stroke, myocardial infarction, or other ischemic or thromboembolic event
within 6 months before first dose)
- Gastrointestinal disorders, including those associated with a high risk of
perforation or fistula formation
- Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon of
red blood or other history of significant bleeding within 12 weeks before first
dose
- Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease
manifestation
- Lesions invading or encasing any major blood vessels except thromboses of
portal/hepatic vasculature attributed to underlying liver disease and/or liver
tumor
- Other clinically significant disorders that would preclude safe study
participation (serious non-healing wound/ulcer/bone fracture;
uncompensated/symptomatic hypothyroidism; known HIV)
- Must not have untreated or incompletely treated varices with bleeding or high risk for
bleeding. Subjects treated with adequate endoscopic therapy (in accordance with
institutional standards) without any episodes of recurrent overt GI bleeding requiring
transfusion or hospitalization for at least 6 months prior to study entry are eligible
- Must not have a psychiatric illness, other significant medical illness, or social
situation (such as involuntary incarceration) which, in the investigator's opinion,
would limit compliance or ability to comply with study requirements
- Women must not be pregnant or breastfeeding since cabozantinib may harm the fetus or
child.
- Women of child-bearing potential (not surgically sterilized and between menarche and
1-year post menopause) and men must agree to use 2 methods of adequate contraception
(hormonal plus barrier or 2 barrier forms) OR abstinence prior to study entry, for the
duration of study participation, and for 4 months following completion of study
therapy. Should a woman become pregnant or suspect she is pregnant while participating
in this study, she should inform her treating physician immediately.
- Prisoners or subjects who are involuntarily incarcerated, or compulsorily detained for
treatment of either a psychiatric or physical (e.g. infectious disease) illness would
be excluded.
- Concomitant treatment with strong inducers or inhibitors of CYP3A4 is not allowed.
Patients must discontinue the drug(s) at least 14 days prior to first study dose on
the study.
- Concomitant anticoagulation with oral anticoagulants (e.g. warfarin, direct thrombin
and factor Xa inhibitors), or platelet inhibitors (e.g. clopidogrel) is not allowed.
- Must not have corrected QT interval calculated by the Fridericia formula (QTcF) > 500
ms per electrocardiogram (ECG) within 28 days before first dose of study treatment.
