Inclusion Criteria:
- PRE-REGISTRATION: Age >= 18 years
- PRE-REGISTRATION: Disease characteristics:
- Radiologically confirmed hepatocellular carcinoma (HCC) that is not eligible for
curative resection, transplantation, or ablative therapies
- Received at least one prior systemic treatment for HCC
- NOTE: Prior radiation, chemoembolization, radioembolization or other local
ablative therapies or hepatic resection are permitted
- PRE-REGISTRATION: Measurable disease by any imaging modality as defined by Response
Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in at least one site not
previously treated with radiation or liver directed therapy (including bland, chemo-
or radio-embolization, or ablation)
- NOTE: Tumor lesions in a previously irradiated area are not considered measurable
disease; disease that is measurable by physical examination only is not eligible
- PRE-REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0,
1 or 2
- PRE-REGISTRATION: Child-Pugh scores of =< 7 (Child-Pugh A or B7)
- PRE-REGISTRATION: Barcelona Clinic Liver Cancer Stage (BCLC) stage A, B, or C
- PRE-REGISTRATION: Able to swallow oral medication
- PRE-REGISTRATION: Willingness to provide mandatory tissue specimens for correlative
research
- REGISTRATION: Tumor tissue must be FGF19 positive by messenger ribonucleic acid (mRNA)
or immunohistochemistry (IHC)
- REGISTRATION: Measurable disease by any imaging modality as defined by RECIST 1.1
criteria in at least one site not previously treated with radiation or liver directed
therapy (including bland, chemo- or radio-embolization, or ablation
- REGISTRATION: ECOG performance status (PS) 0, 1 or 2
- REGISTRATION: Absolute neutrophil count (ANC) >= 1500/mm^3 (=< 15 days prior to
registration)
- REGISTRATION: Hemoglobin >= 9.0 g/dL (=< 15 days prior to registration)
- REGISTRATION: Platelet count >= 75,000/mm^3 (=< 15 days prior to registration)
- REGISTRATION: Albumin >= 2.5 g/dL (=< 15 days prior to registration)
- REGISTRATION: Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 2.5 x
upper limit of normal (ULN) (or =< 5 x ULN for patients with liver metastasis) (=< 15
days prior to registration)
- REGISTRATION: Total bilirubin =< 1.5 x ULN (=< 15 days prior to registration)
- REGISTRATION: Phosphorus =< 1.5 x ULN (=< 15 days prior to registration)
- REGISTRATION: Calcium =< 1.5 x ULN (=< 15 days prior to registration)
- REGISTRATION: Prothrombin time/international normalized ratio/activated partial
thromboplastin time (PT/INR/aPTT) =< 1.5 x ULN OR if patient is receiving
anticoagulant therapy then INR or aPTT is within target range of therapy (=< 15 days
prior to registration)
- REGISTRATION: Serum creatinine =< 1.5 x ULN (=< 15 days prior to registration)
- REGISTRATION: Calculated creatinine clearance >= 40 ml/min using the Cockcroft-Gault
formula (=< 15 days prior to registration)
- REGISTRATION: Child-Pugh scores of =< 7 (Child-Pugh A or B7)
- REGISTRATION: Negative pregnancy test done =< 7 days prior to registration, for
persons of childbearing potential only
- REGISTRATION: Willing to use an adequate method of contraception from registration
through 120 days after the last dose of study medication
- NOTE: Only for persons of childbearing potential or persons able to father a
child with partners of childbearing potential
- REGISTRATION: Able to swallow oral medication
- REGISTRATION: Provide written informed consent
- REGISTRATION: Willingness to provide mandatory blood specimens for correlative
research
- REGISTRATION: Willingness to provide mandatory tissue specimens for correlative
research
- REGISTRATION: Willingness and the ability to comply with scheduled visits (including
geographical proximity), treatment plans, laboratory tests, and other study procedures
- REGISTRATION: Ability to complete questionnaires by themselves or with assistance
Exclusion Criteria:
- PRE-REGISTRATION: Known standard therapy for the patient's disease that is potentially
curative or definitely capable of extending life expectancy
- PRE-REGISTRATION: Prior organ transplantation
- PRE-REGISTRATION: History of untreated brain metastasis
- PRE-REGISTRATION: History of hepatitis B (HBV) and viral load >=100 IU/mL
- NOTE: Patients who have received antiviral therapy and have viral load < 100
IU/mL are eligible
- PRE-REGISTRATION: History and/or current evidence of any of the following disorders:
- Non-tumor related alteration of the calcium-phosphorus homeostasis that is
considered clinically significant in the opinion of the Investigator
- Ectopic mineralization/calcification, including but not limited to soft tissue,
kidneys, intestine, or myocardia and lung, considered clinically significant in
the opinion of the Investigator
- Retinal or corneal disorder confirmed by retinal/corneal examination and
considered clinically significant in the opinion of the Investigator
- PRE-REGISTRATION: Co-morbid systemic illnesses or other severe concurrent disease
which, in the judgment of the investigator, would make the patient inappropriate for
entry into this study or interfere significantly with the proper assessment of safety
and toxicity of the prescribed regimens
- PRE-REGISTRATION: History or risk of autoimmune disease, including, but not limited
to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease,
vascular thrombosis associated with antiphospholipid syndrome, Wegener's
granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis,
autoimmune thyroid disease, vasculitis, or glomerulonephritis. Notes:
- Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid
replacement hormone are eligible
- Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are
eligible
- Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis would
be excluded) are permitted provided that they meet the following conditions:
- Patients with psoriasis must have a baseline ophthalmologic exam to rule out
ocular manifestations
- Rash must cover less than 10% of body surface area (BSA)
- Disease is well controlled at baseline and only requiring low potency
topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%,
flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
- No acute exacerbations of underlying condition within the last 6 months (not
requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate,
retinoids, biologic agents, oral calcineurin inhibitors; high potency or
oral steroids)
- PRE-REGISTRATION: Known active human immunodeficiency virus (HIV) infection (defined
as patients who are not on anti-retroviral treatment and have detectable viral load
and CD4+ < 500/ml). NOTE: HIV positive patients who are well controlled on
anti-retroviral therapy are allowed to enroll
- PRE-REGISTRATION: Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active severe infection. NOTE: Must be afebrile > 7 days to be
eligible. Patient may be eligible if fever is present and infection has been
ruled out or fever is related to tumor
- Psychiatric illness/social situations that would limit compliance with study
requirements
- PRE-REGISTRATION: Receiving any other investigational agent which would be considered
as a treatment for the primary neoplasm
- PRE-REGISTRATION: Other active malignancy < 6 months prior to registration
- EXCEPTIONS: Non-melanotic skin cancer, papillary thyroid cancer, or
carcinoma-in-situ of the cervix, or others curatively treated and now considered
to be at less than 30% risk of relapse are eligible
- PRE-REGISTRATION: Clinically significant or uncontrolled cardiac disease, including
unstable angina, acute myocardial infarction within 6 months from day 1 of study
treatment administration, New York Heart Association class III and IV congestive heart
failure, and uncontrolled arrhythmia
- NOTE: Participants with pacemaker or with atrial fibrillation and well controlled
heart rate are allowed
- PRE-REGISTRATION: History of pneumonitis or interstitial lung disease within =< 3
years prior to pre-registration
- REGISTRATION: Known standard therapy for the patient's disease that is potentially
curative or definitely capable of extending life expectancy
- REGISTRATION: Any of the following because this study involves an investigational
agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and
newborn are unknown:
- Pregnant persons
- Nursing persons
- Persons of childbearing potential who are unwilling to employ adequate
contraception
- REGISTRATION: Any of the following prior therapies:
- Surgery =< 4 weeks prior to registration
- Radiotherapy for extended field =< 4 weeks prior to registration or limited field
radiotherapy =< 2 weeks prior to registration
- Systemic anticancer therapy =< 2 weeks prior to registration
- NOTE: Prior immunotherapy is allowed unless patient discontinued due to
grade 4 adverse event (AE)
- Live vaccine =< 30 days prior to registration
- Prior treatment with FGFR inhibitor
- Received strong inhibitors and inducers and sensitive substrates of CYP3A4 =< 2
weeks prior to registration
- Received a drug that has not received regulatory approval for any indication as
follows:
- =< 2 weeks prior to registration for nonmyelosuppressive agents or
- =< 4 weeks prior to registration for myelosuppressive agents
- REGISTRATION: History and/or current evidence of any of the following disorders:
- Retinal or corneal disorder confirmed by retinal/corneal examination and
considered clinically significant in the opinion of the Investigator
- REGISTRATION: Active central nervous system (CNS) metastasis and/or carcinomatous
meningitis
- NOTE: Patients with previously treated brain metastases that are clinically and
radiologically stable (for at least 4 weeks prior to enrollment) are eligible
- REGISTRATION: History of hepatitis B (HBV) and viral load >= 100 IU/ml
- NOTE: Patients who have received antiviral therapy and have viral load < 100
IU/ml are eligible
- REGISTRATION: Corrected QT interval using Fridericia's formula (QTcF) > 480 msec
- NOTE: Patients with an atrioventricular pacemaker or other condition (for
example, right bundle branch block) that renders the QT measurement invalid are
an exception and the criterion does not apply
- REGISTRATION: Co-morbid systemic illnesses or other severe concurrent disease which,
in the judgment of the investigator, would make the patient inappropriate for entry
into this study or interfere significantly with the proper assessment of safety and
toxicity of the prescribed regimens
- REGISTRATION: Receiving any other investigational agent which would be considered as a
treatment for the primary neoplasm
- REGISTRATION: History or risk of autoimmune disease, including, but not limited to,
systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease,
vascular thrombosis associated with antiphospholipid syndrome, Wegener's
granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis,
autoimmune thyroid disease, vasculitis, or glomerulonephritis. Notes:
- Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid
replacement hormone are eligible.
- Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are
eligible.
- Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis would
be excluded) are permitted provided that they meet the following conditions:
- Patients with psoriasis must have a baseline ophthalmologic exam to rule out
ocular manifestations
- Rash must cover less than 10% of body surface area (BSA)
- Disease is well controlled at baseline and only requiring low potency
topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%,
flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
- No acute exacerbations of underlying condition within the last 12 months
(not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate,
retinoids, biologic agents, oral calcineurin inhibitors; high potency or
oral steroids)
- REGISTRATION: Known active human immunodeficiency virus (HIV) infection (defined as
patients who are not on anti-retroviral treatment and have detectable viral load and
CD4+ < 500/ml)
- NOTE: HIV-positive patients who are well controlled on anti-retroviral therapy
are allowed to enroll
- REGISTRATION: Currently taking strong CYP3A inhibitors/inducers and unable to
discontinue =< 7 days prior to registration
