PRIMARY OBJECTIVE:
I. Evaluation of safety and tolerability of an autologous dendritic cell (DC) vaccine
delivered by intra-tumoral injection in patients with primary liver cancer treated with
high-dose conformal external beam radiotherapy (EBRT).
SECONDARY OBJECTIVES:
I. To assess feasibility in patients with liver cancer treated with high-dose conformal EBRT
followed by autologous DC vaccine injection.
II. To assess overall response rate in patients with liver cancer treated with high-dose
conformal EBRT followed by autologous DC vaccine injection.
III. To assess progression free survival in patients with liver cancer treated with high-dose
conformal EBRT followed by autologous DC vaccine injection.
IV. To assess clinical benefit rate in patients with liver cancer treated with high-dose
conformal EBRT followed by autologous DC vaccine injection.
V. To assess time to response in patients with liver cancer treated with high-dose conformal
EBRT followed by autologous DC vaccine injection.
VI. To assess duration of response in patients with liver cancer treated with high-dose
conformal EBRT followed by autologous DC vaccine injection.
VII. To assess overall survival in patients with liver cancer treated with high-dose
conformal EBRT followed by autologous DC vaccine injection.
RADIOLOGIC STUDY OBJECTIVE:
I. To assess the radiologic response over time of primary liver tumors treated with high-dose
conformal EBRT followed by autologous DC vaccine injection.
CORRELATIVE RESEARCH OBJECTIVES:
I. To monitor patients' immune response after vaccine therapy. II. To assess the immune
response to pneumococcal 13-valent conjugate vaccine (Prevnar).
OUTLINE:
Patients undergo standard of care high-dose EBRT for 5 or 15 fractions over 1-3 weeks (cycle
1). Patients then receive autologous dendritic cells intratumorally (IT) on day 1 of cycles
2-8, and pneumococcal 13-valent conjugate vaccine intramuscularly (IM) on day 1 of cycles 2-4
only. Treatment repeats every 28 days for up to 7 cycles in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 2 weeks and then every 3
months for 1 year (beginning at week 36 or 12 weeks after last autologous dendritic cell dose
whichever is earlier). Patients are then followed every 3 months until disease progression,
and then every 6 months until 5 years after registration.
Inclusion Criteria:
- Histological and/or radiologic confirmation of hepatocellular carcinoma (HCC) OR
histologic confirmation of intrahepatic cholangiocarcinoma (CCA)
- The following tumor characteristics must be met
- Unresectable HCC or intrahepatic CCA
- Measurable or evaluable disease
- All lesions should be treatable by EBRT while meeting normal tissue constraints
- Tumor lesions should be accessible using an ultrasound (US) guided approach for
intratumoral DC injection
- Patients are required to have no evidence of extrahepatic tumor (excluding tumor
thrombus) by computed tomography (CT) or magnetic resonance imaging (MRI) scan
- NOTE: Patients who are not candidates for surgical treatment or for ablation
with curative intent are allowed
- Good candidate for standard of care high-dose conformal EBRT in the view of the
investigator
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to
registration)
- Absolute lymphocyte count (ALC) >= 500/mm^3 (obtained =< 14 days prior to
registration)
- Absolute monocyte count (AMC) >= 300/mm^3 (obtained =< 14 days prior to registration)
- Platelet count >= 50,000/mm^3 (obtained =< 14 days prior to registration)
- Hemoglobin >= 9.0 g/dL (obtained =< 14 days prior to registration)
- Total bilirubin < 3 mg/dL (obtained =< 14 days prior to registration)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 x upper limit
of normal (ULN) (obtained =< 14 days prior to registration)
- Creatinine =< 2 mg/dL (obtained =< 14 days prior to registration)
- Prothrombin time/international normalized ratio (PT/ INR) =< 1.5 x ULN (obtained =< 14
days prior to registration)
- Negative pregnancy test done =< 7 days prior to registration, for persons of
childbearing potential only
- Ability to provide written consent
- Willingness to return to enrolling institution for follow-up (during the active
monitoring phase of the study)
- Willingness to provide blood and tissue samples for correlative research purposes
Exclusion Criteria:
- 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
- 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
- Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)
positive and currently receiving antiretroviral therapy
- NOTE: Patients known to be HIV positive, but without clinical evidence of an
immunocompromised state, are eligible for this trial
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements
- Receiving any other investigational agent that would be considered a treatment for the
primary neoplasm
- Other active malignancy =< 3 years prior to registration. EXCEPTIONS: Non-melanotic
skin cancer or carcinoma-in-situ of the cervix
- NOTE: If there is a history of prior malignancy, they must not be receiving other
specific treatment for their cancer
- Major surgery =< 4 weeks prior to enrollment (other than diagnostic surgery or
surgical spacer placement in preparation for radiation treatment)
- History of hypersensitivity or anaphylactoid reactions to pneumococcal vaccine or any
component of the formulation, including diphtheria toxoid
- Active autoimmune disease such as autoimmune hepatitis, Crohn's disease, rheumatoid
arthritis, Sjogren's disease, systemic lupus erythematosus, or similar conditions
- Requires coagulopathy treatment (INR > 1.5) or use of anti-platelet agents that cannot
be discontinued for the intratumoral injection procedure
- NOTE: Heparin for line patency without detectable lab abnormalities in
coagulation will be allowed
- Corticosteroids =< 2 weeks prior to registration, including oral, intravenous (IV),
subcutaneous, or inhaled routes of administration
- NOTE: Patients on chronic corticosteroids for adrenal insufficiency or other
reasons may enroll if they receive less than 10 mg/day of prednisone (or
equivalent)
- History of myocardial infarction =< 6 months, or congestive heart failure requiring
use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- Child Pugh class B or C cirrhosis of the liver
- Previously received immune modulating therapies including but not limited to immune
checkpoint inhibitors targeting PD-1 PDL-1 CTLA4, etc; or prior dendritic cell therapy
- Prior liver radiation, including radioembolization
- Barcelona Clinic Liver Cancer (BCLC) stage D disease
