Apatinib Plus Camrelizumab in Patients With Previously Treated Advanced Biliary Tract Cancer

Exclusion Criteria

• •2. Patients must have failed or are intolerant to one line of systemic chemotherapy treatment.
• •3. 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.
• •4. Age ≥ 18 years.
• •5. Eastern Cooperative Oncology Group (ECOG) Performance Status Assessment of 0-2.
• •6. Life expectancy of at least 12 weeks (3 months).
• •7. Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure. Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other study requirements.
• •8. 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.
• •9. For patients with advanced biliary tract cancer, liver function status Child-Pugh Class A or B (score\<=7).
• •1. Subjects with active CNS metastases are excluded. If CNS metastases are treated and subjects 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. Subjects must be off corticosteroids or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
• •2. Subjects with active, known or suspected autoimmune disease. Subjects 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
• •3. Subjects with 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.
• •4. 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 \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)\].
• •5. Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
• •6. Child Pugh C disease
• •7. History of severe hypersensitivity reactions to other monoclonal antibodies
• •8. History of allergy or intolerance to study drug components or Polysorbate-80-containing infusions
• •9. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
• •10. History or concurrent condition of interstitial lung disease of any grade or severely impaired pulmonary function.
• •11. Unresolved toxicity higher than CTCAE grade 1 attributed to any prior therapy/procedure excluding alopecia.
• •12. 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 result must be documented before start of treatment.
• •13. Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study.
• •14. Anticancer chemotherapy during the study or within 4 weeks of study enrollment. Subjects 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.
• •15. Hormonal therapy during the study or within 2 weeks of first study enrollment.
• •16. Investigational drug therapy outside of this trial during or within 4 weeks of first study treatment.
• •17. Notably, patients with severe esophageal varices or presented with positive fecal occult blood were also excluded.