Study to Evaluate the Efficacy and Safety of Immunotherapy With Axitinib in Advanced Collecting Duct Carcinoma

Inclusion Criteria24

• Fully understand and be willing to provide written informed consent.
• Male or female with age ≥ 18 years and \<80 years.
• Have received prior systemic therapy after previous metastasis for collecting duct carcinoma, histologically confirmed diagnosis of unresectable, recurrent or metastatic collecting duct carcinoma.
• Having at least one measurable disease per RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if re-progression has been demonstrated.
• ECOG PS 0 or 1.
• Adequate function of vital organs:
• Bone marrow function (without blood or blood products transfusion, without hematopoietic stimulating factor or other medication to improve blood cell count within 2 days prior to first dose of study drug): Absolute neutrophil count (ANC) ≥ 1.5×109/L. Platelets ≥ 100×109/L. Hemoglobin ≥ 9.0g/dL or ≥ 5.6mmol/L. 6.2 Renal function: Serum creatinine ≤ 1.5×ULN 6.3 Hepatic function:Serum total bilirubin ≤1.5×ULN or total bilirubin levels \>1.5×ULN with direct bilirubin ≤ ULN. AST and ALT ≤2.5 × ULN, ≤5×ULN in those with hepatic metastasis.
• Endocrine function: Normal thyroid stimulating hormone, or abnormal TSH whilst normal FT3 and FT4.
• Coagulation function: International normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN, and activated partial thromboplastin time (aPTT) ≤1.5×ULN, Subjects receiving anticoagulant therapy (e.g., heparin or warfarin) may participate in the study with PT or APTT levels within the scope of the proposed therapy and monitored during study treatment.
• Left ventricular ejection fraction (LVEF) ≥ 50%.
• Being willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
• Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first treatment dose. Female subjects of childbearing potential and male subjects whose partners are of childbearing potential must agree to use a highly effective methods of contraceptive throughout the study and for 180 days after the last dose of study therapy.
• \. Poorly controlled hypertension (systolic blood pressure ≥ 150mmHg and/or diastolic blood pressure ≥ 90mmHg).
• \. Presence of the following cardiovascular events within 6 months prior to randomization: Myocardial infarction Unstable angina pectoris Cardiac angioplasty or stent Coronary/peripheral artery bypass graft Grade III or IV congestive heart failure per New York Heart Association Cerebrovascular accident or transient ischemic attack QT interval (QTc) ≥ 480 msec corrected with heart rate (Bazett's formula); 14. Has active hemorrhage or history of other significant hemorrhage episodes within 30 days prior to randomization.
• \. Has deep vein thrombosis or pulmonary embolism within 6 months prior to randomization.
• \. Has arterial thrombosis within 12 months prior to randomization. 17. Has clinically significant gastrointestinal (GI) abnormalities including: Malabsorption, total gastrectomy or any other condition that might affect the absorption of orally taken medication.
• Active ulcer under treatment in the past 6 months; Active GI bleeding (e.g., hematemesis, hematochezia or melena) in the past 3 months, and without evidence of resolution documented by endoscopy or colonoscopy.
• Intraluminal metastatic lesion with suspected hemorrhage, inflammatory bowel disease, ulcerative colitis, GI perforation, or other GI conditions associated with increased risk of perforation.
• \. Has a history of or current (non-infective) pneumonia/ interstitial lung disease that required steroids.
• \. Has an active infection requiring systemic therapy. Has a known history of Human Immunodeficiency Virus (HIV) infection (HIV antibody positive), HBV or HCV infection (Patients with positive HBsAg or negative HBsAg, but positive HBcAb will be enrolled in the study when HBV DNA was tested in central laboratory and lower than ULN. Patients with a history of HCV infection may participate in the study if the result of HCV RNA test was negative during screening period).
• \. Has received a live virus vaccine within 30 days prior to randomization, including (but not limited to) mumps, rubella, measles, varicella/ herpes zoster (chicken pox), yellow fever, rabies, Bacille Calmette-Guérin (BCG) and typhoid vaccine. Inactivated virus vaccines are allowed.
• \. Has a history of hypersensitivity reaction, including (but not limited to) antibodies and TKIs.
• \. Known history of psychiatric disorders or drug abuse. 23. Has evidence of inadequate wound healing. 24. Has current use (within 7 days of randomization) or anticipated need for treatment drugs what are known strong CYP3A4/5 inhibitor and CYP3A4/5 inducer (including, but not limited to, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin and St. John's wort) or the drugs that are known with proarrhythmic potential (including, but not limited to, terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol and benazapril, etc.).
• \. Has a history or current evidence on any condition, therapy or laboratory abnormality that might confound the results of the study, interfere with subject's participation for the full duration of the study, or is not in the best interest of subject to participate, in the opinion of investigators.