| Eligibility |
Inclusion Criteria:
- Must have histologically or cytologically documented carcinoma primary to the intra-
or extra-hepatic biliary system or gall bladder with clinical and/or radiologic
evidence of unresectable, locally advanced or metastatic disease. Patients with
ampullary carcinoma are not eligible.
- Must have failed or are intolerant to one line of systemic treatment but no more than
2 prior lines of systemic chemotherapy for advanced BTC. Patients who received
adjuvant chemotherapy and had evidence of disease recurrence within 6 months of
completion of the adjuvant treatment are also eligible. If the patient received
adjuvant treatment and had disease recurrence after 6 months, patients will only be
eligible after failing or having intolerance to one line of systemic chemotherapy used
to treat the disease recurrence.
- Age = 18
- Eastern Cooperative Oncology Group (ECOG) Performance Status Assessment of 0 or 1.
- Must have radiographic measurable disease per Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1.
- Life expectancy of at least 12 weeks (3 months).
- For patients who have received prior radiation, cryotherapy, radiofrequency ablation,
therasphere, ethanol injection, transarterial chemoembolization (TACE) or photodynamic
therapy, the following criteria must be met: 28 days have elapsed since that therapy;
Lesions that have not been treated with local therapy must be present and measureable.
- Must be able to understand and be willing to sign the written informed consent form.
Must be willing and able to comply with scheduled visits, treatment schedule,
laboratory testing, and other study requirements.
- All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 1
or less at the time of signing the Informed Consent Form (ICF) except for alopecia.
- Adequate bone marrow, liver and liver function.
- Women of childbearing potential must have a negative serum or urine pregnancy test
(minimum sensitivity of 25 IU/L or equivalent units of HCG) performed within24 hours
prior to the start of nivolumab Post-menopausal women (defined as no menses for at
least 1 year) and surgically sterilized women are not required to undergo a pregnancy
test.
- Men and women of childbearing potential must agree to use adequate contraception
beginning at the signing of the ICF until at least 3 months after the last dose of
study drug.
- Patients with history of hepatitis B and hepatitis C will be eligible but patients
with hepatitis B must be started on antiviral therapy prior to beginning study
therapy.
- Availability of archival tumor tissue for biomarkers analysis (FFPE block or cell
block will be required).
Exclusion Criteria:
- Active central nervous system (CNS). If CNS metastases are treated and potential
participants are at neurologic baseline for at least 2 weeks prior to enrollment, they
will be eligible but will need a Brain MRI prior to enrollment. Must be off
corticosteroids or on a dose of less than 10 mg per day.
- Active, known or suspected autoimmune disease. Potential participants with vitiligo,
type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only
requiring hormone replacement, or conditions not expected to recur in the absence of
an external trigger are permitted to enroll.
- A condition requiring systemic treatment with either corticosteroids (>10 mg daily
prednisone equivalent) or other immunosuppressive medications within 14 days of
enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg
daily prednisone equivalent, are permitted in the absence of active autoimmune
disease.
- Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4
antibody (including ipilimumab or any other antibody or drug specifically targeting
T-cell costimulation or checkpoint pathways).
- Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for
curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial
bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades
lamina propria)].
- Known history of human immunodeficiency virus (HIV) infection or acquired
immunodeficiency syndrome (AIDS).
- Child Pugh B or C disease.
- History of severe hypersensitivity reactions to other monoclonal antibodies.
- History of allergy or intolerance to study drug components or
Polysorbate-80-containing Infusions.
- Substance abuse, medical, psychological or social conditions that may interfere with
the patient's participation in the study or evaluation of the study results.
- History or concurrent condition of interstitial lung disease of any grade or severely
impaired pulmonary function.
- Unresolved toxicity higher than CTCAE grade1 attributed to any prior therapy/procedure
excluding alopecia.
- Pregnant or breast-feeding patients. Women of childbearing potential must have a
negative serum or urine pregnancy test (minimum sensitivity of 25 IU/L or equivalent
units of HCG) performed within 24 hours prior to the start of nivolumab and a negative
results must be documented before start of treatment.
- Any illness or medical conditions that are unstable or could jeopardize the safety of
the patient and his/her compliance in the study.
- Excluded Therapies and Medications for Cancer: 1) Anticancer chemotherapy during the
study or within 4 weeks of study enrollment. Must have recovered from the toxic
effects of the previous anti-cancer chemotherapy (with the exception of alopecia).
Anti-cancer therapy is defined as any agent or combination of agents with clinically
proven anti-tumor activity administered by any route with the purpose of affecting the
malignancy, either directly or indirectly, including palliative and therapeutic
endpoints. 2) Hormonal therapy during the study or within 2 weeks of first study
enrollment. 3) Radiotherapy to target lesions during study or within 2 weeks of
enrollment. 4) An irradiated lesion is considered evaluable only if it has shown
enlargement since the completion of last radiation. 5) Bone marrow transplant or stem
cell rescue. 6) Investigational drug therapy outside of this trial during or within 4
weeks of first study treatment.
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