Study of Nivolumab in Patients With Advanced Refractory Biliary Tract Cancers
Condition: Biliary Tract Cancer; Biliary Tract Neoplasms
MeSH terms: Biliary Tract Neoplasms
Intervention: Nivolumab
Intervention description: Participants will receive nivolumab at a dose of 240 mg intravenously (IV) every 2 weeks (Q 2W) for 16 weeks (16W) and then 480 every 4 weeks (Q4W) from 17 weeks to end of study.
Intervention MeSH terms: Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: advanced biliary tract cancer; refractory biliary tract cancer; digestive diseases; immunotherapy

Summary:

      This research study is designed to see if a drug called Nivolumab is effective in treating
      patients with advanced refractory biliary tract cancers. Nivolumab has been approved by the
      U.S. Food and Drug Administration (FDA) for treatment of certain types of cancer but is not
      approved by the FDA for treatment of your type of cancer.
    

Eligibility criteria:

        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.