| Eligibility |
Inclusion Criteria:
- Patient or legally authorized representative must be able to understand and willing to
sign an IRB approved written informed consent document.
- Patients must be 18 years or older
- Patient must have histological or radiographically confirmed unresectable or
metastatic hepatocellular carcinoma.
- Patients must have no concomitant active oncologic diagnosis
- Patient must have at least one radiographically measurable lesion defined as
non-radiated lesions that can be accurately measured in at least one dimension
(longest diameter to be recorded) as greater than or equal to 10mm with calipers by
radiographic exam. Further details listed in section 5.5.
- Patient must have received no previous systemic or investigational therapy for the
treatment of HCC. Patients who previously received locoregional therapies remain
eligible for this study.
- Patient must have a life expectancy of minimum 3 months.
- Patient must have normal bone marrow and organ function as defined below.
- Absolute neutrophil count >1,500/mcl
- Platelets >75,000/ul without transfusion
- Hemoglobin >9.0 g/dL
- Creatinine should be below the upper limit of normal OR
- Creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above
institutional normal
- Aspartate aminotransferase (AST), Alanine transaminase (ALT), and alkaline
phosphatase (ALP) <5 times the upper limit of normal
- Serum bilirubin no greater than 1.5-2x the upper limit of normal
- Patient not on anticoagulation must have international Normalized Ratio (INR) and
activated partial thromboplastin time (PTT) <1.7 upper limit of normal. Patients on
anticoagulation may be included, provided they can be off anticoagulation as indicated
for paired biopsy collection.
- Patient will have an ECOG performance status of 0 or 1
- Patient must consent for baseline and on treatment biopsies, if prior baseline
biopsies have been performed, and stored within the University of Rochester Cancer
Library, then baseline biopsies are not necessary.
- Patients must be Child-Pugh class A or less
- Female subjects of childbearing potential must demonstrate a negative urine or serum
pregnancy test.
- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) for a duration consistent
with that described in the Bevacizumab and Atezolizumab labels (i.e. 6 months). Should
a woman become pregnant or suspect she is pregnant while participating in this study,
she must inform her treating physician immediately.
- Male subjects with a female partner of child-bearing potential must agree to use 2
adequate methods of contraception (barrier + hormonal for example).
Exclusion Criteria:
- Patient with any histologic variant of HCC such as fibrolamellar, sarcomatous, or
mixed cholangiocarcinoma and HCC.
- Patient has a history of other malignancy = 3 years previous with the exception of
basal cell or squamous cell carcinoma of the skin which were treated with local
resection only, carcinoma in situ of the cervix, or prostate cancer that does not
require treatment.
- Patient who received a previous systemic therapy for hepatocellular carcinoma or has
tumor recurrence sooner than 6 months after completion of the last dose of therapy.
- Patient who is receiving any other investigational agent
- Patient has a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to PXS-5505, Atezolizumab, or Bevacizumab
- Patient with uncontrolled intercurrent illness including, but not limited to, ongoing
or active infection symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, any clinically active malabsorption syndrome, inflammatory bowel
disease, any condition that increases the risk of severe gastrointestinal toxicity, or
psychiatric illness/social situations that would limit compliance with study
requirements
- Has current active autoimmune disease, or a documented history of autoimmune disease
or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects
with vitiligo, resolved childhood asthma/atopy, hypothyroidism on thyroid
supplementation, and type 1 diabetics would be exception to this rule.
- Patients who are eligible for liver transplantation
- Has had an allogenic tissue/solid organ transplant.
- Has interstitial lung disease or a history of pneumonitis that required oral or
intravenous glucocorticoids to assist with management.
- Has received or plans to receive a live vaccine within 30 days prior to the first
administration of study medication. Flu vaccines that do not contain live virus are
permitted.
- Has known active Hepatitis B or C.
- Untreated or incompletely treated esophageal and/or gastric varices with bleeding or
high-risk for bleeding
- A prior bleeding event due to esophageal and/or gastric varices within 6 months prior
to initiation of study treatment.
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures
- Inadequately controlled arterial hypertension
- Prior history of hypertensive crisis or hypertensive encephalopathy
- Evidence of bleeding diathesis or significant coagulopathy
- Inability to tolerate oral medications
- Child Pugh B or C cirrhosis
- Known connective tissue disorder
- Evidence of vascular aneurysmal disease
- History of myeloproliferative, myelodysplastic disorders, or monoclonal gammopathy of
undetermined significance
- Major surgery within 4 weeks of enrollment
- Patient who is pregnant and/or breastfeeding.
|
