| Eligibility |
Inclusion Criteria:
- Written informed consent obtained.
- Age = 18 years at time of study entry.
- Advanced ICC with diagnosis confirmed by histology or cytology.
- Patients with no prior systemic chemotherapy or targeted therapy or loco-regional
therapy (including but not limited to transarterial chemoembolization, transarterial
embolization, transarterial chemotherapy or transarterial radioembolization) or
immunotherapy for ICC. Patients with recurrent disease more than 6 months after
completion of adjuvant chemotherapy following curative resection are eligible.
- At least one measurable site of disease as defined by RECIST v1.1 with spiral CT scan
or MRI.
- Performance status (PS) = 2 (ECOG scale).
- Life expectancy of at least 12 weeks.
- Adequate blood count, liver-enzymes, and renal function: absolute neutrophil count =
1,500/L, platelets =75 x103/L; Total bilirubin = 3x upper normal limit; Aspartate
Aminotransferase (SGOT), Alanine aminotransferase (SGPT) = 5 x upper normal limit
(ULN); International normalized ratio (INR) =1.25; Albumin = 31 g/dL; Serum Creatinine
= 1.5 x institutional ULN or creatinine clearance (CrCl) = 30 mL/min (if using the
Cockcroft-Gault formula )
- Female patients with reproductive potential must have a negative urine or serum
pregnancy test within 7 days prior to start of trial.
- Subject is willing and able to comply with the protocol for the duration of the study
including undergoing treatment, adherence to contraceptive measures, scheduled visits
and examinations including follow up.
Exclusion Criteria:
- Diagnosis of hepatocellular carcinoma (HCC), mixed cholangiocarcinoma and HCC,
sarcomatoid hepatocellular carcinoma, or hepatic fibrolamellar carcinoma by histology
or cytology.
- Uncontrolled pericardial effusion, pleural effusion, or clinically significant
moderate or severe ascites that is symptomatic or requires thoracentesis or
paracentesis during the screening phase for control of symptoms.
- History of cardiac disease, including clinically significant gastrointestinal bleeding
within 4 weeks prior to start of study treatment.
- Thrombotic or embolic events such as cerebrovascular accident (including transient
ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months
Prior to the first dose of study drug with the exception of thrombosis of a segmental
portal vein.
- Prior treatment with cryoablation.
- Major surgery within 4 weeks of starting the study treatment OR subjects who have not
recovered from effects of major surgery.
- Patients with second primary cancer, except adequately treated basal skin cancer or
carcinoma in-situ of the cervix.
- Immunocompromised patients, e.g. patients who are known to be serologically positive
for human immunodeficiency virus (HIV).
- Any condition or comorbidity that, in the opinion of the investigator, would interfere
with evaluation of study Treatment or interpretation of patient safety or study
results, including but not limited to:
1. history of interstitial lung disease
2. Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection (i.e double
infection)
3. known acute or chronic pancreatitis
4. active tuberculosis
5. any other active infection (viral, fungal or bacterial) requiring systemic
therapy
6. history of allogeneic tissue/solid organ transplant
7. diagnosis of immunodeficiency or patient is receiving chronic systemic steroid
therapy or any other form of immunosuppressive therapy within 7 days prior to the
first dose of Sintilimab treatment.
8. Has an active autoimmune disease requiring systemic treatment within the past 3
months or a documented history of clinically severe autoimmune disease, or a
syndrome that requires systemic steroids or immunosuppressive agents. Exceptions:
Subjects with vitiligo, hypothyroidism, diabetes mellitus type I or resolved
childhood asthma/atopy are an exception to this rule. Subjects that require
intermittent use of bronchodilators or local steroid injections would not be
excluded from the study. Subjects with Hashimoto thyroiditis, hypothyroidism
stable on hormone replacement or psoriasis not requiring treatment are not
excluded from the study.
9. Live vaccine within 30 days prior to the first dose of Sintilimab treatment or
during study treatment.
10. History or clinical evidence of Central Nervous System (CNS) metastases
Exceptions are: Subjects who have completed local therapy and who meet both of
the following criteria: I. are asymptomatic and II. have no requirement for
steroids 6 weeks prior to start of Tislelizumab treatment. Screening with CNS
imaging (CT or MRI) is required only if clinically indicated or if the subject
has a history of CNS
- Medication that is known to interfere with any of the agents applied in the trial.
- Any other efficacious cancer treatment except protocol specified treatment at study
start.
- Female subjects who are pregnant, breast-feeding or male/female patients of
reproductive potential who are not employing an effective method of birth control
(failure rate of less than 1% per year). [Acceptable methods of contraception are:
implants, injectable contraceptives, combined oral contraceptives, intrauterine
pessars (only hormonal devices), sexual abstinence or vasectomy of the partner]. Women
of childbearing potential must have a negative pregnancy test (serum ß-HCG) at
screening.
- Patient with any significant history of non-compliance to medical regimens or with
inability to grant reliable informed consent.
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