anlotinib plus sintilimab as first-line treatment for advanced non clear cell renal cell carcinoma

Conditions: Non Clear Cell Renal Carcinoma

Summary: the combination of immune checkpoint inhibitors (icis) plus angiogenesis inhibitors has demonstrated significant anti-tumor activity in certain cancer. the goal of this study was to evaluate the efficacy and safety of sintilimab (a human programmed death-1 ici) plus anlotinib (a multi-target tyrosine kinase inhibitor, inhibiting tumor angiogenesis and proliferative signaling) in advanced non clear cell renal cell carcinoma.


Eligibility criteria:
inclusion criteria: * subjects voluntarily joined the study and signed informed consent; * aged \> 18 years; * ecog body status score is 0 or 1,expected survival time is greater than 3 months. * locally advanced or metastatic, histological confirmed, non-clear cell rcc of all subtypes. patients must have advanced non-clear cell of one of the following subtypes: papillary, chromophobe, collecting duct carcinoma (cdc), renal medullary carcinoma (rmc), or unclassified. * patients must have measurable lesions as defined by the recist 1.1 standard; * adequate hematologic and end-organ function as defined by the following laboratory results obtained within 28 days prior to the first study treatment: 1. absolute neutrophil count (anc) ≥1.5x 109/l 2. lymphocyte count ≥ 500/ul. 3. platelet count ≥ 80x109/l. 4. hemoglobin ≥ 80 g/l (patients may be transfused to meet this criterion). 5. aspartate aminotransferase (ast) and alanine aminotransferase (alt) ≤ 2.5 x upper limit of normal (uln) with the following exceptions: patients with documented liver/bone metastases should have ast and alt ≤ 5 x uln. 6. serum bilirubin ≤ 1.5 x uln. 7. creatinine clearance ≥ 60 ml/min. 8. for female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective forms of contraception and to continue its use 4 weeks after the last dose of anlotinib or sintilimab. * signed informed consent form. * ability and capacity to comply with study and follow-up procedures. exclusion criteria: * those who are known to be allergic to pharmaceutical ingredients. * receive anti-tumor monoclonal antibody or other research drugs within 4 weeks before enrollment; have received other anti-pd-1 antibody therapy or other treatment for pd-1/pd-l1; * previous use of anlotinib or other angiogenesis inhibitors * the patient has any active autoimmune disease or a history of autoimmune disease; * there are uncontrolled heart clinical symptoms or diseases; * patients with congenital or acquired immune deficiency; * receive chemotherapy, targeted therapy, radiotherapy within 2 weeks before enrollment; * a history of gastrointestinal perforation or major surgery within 4 weeks before enrollment; * overactive/venous thrombosis occurred within 6 months prior to enrollment, such as cardiovascular-cerebral vascular (including transient ischemic attack),deep vein thrombosis (except for patients who have recovered from venous catheterization due to previous chemotherapy)and pulmonary embolism; * those with active bleeding or bleeding tendency; * presence of a drug uncontrolled hypertension; * urine routine indicates more than urinary protein 2+; * correct qt interval \> 470msec; if the patient has a prolonged qt interval, but the investigator's study evaluates that the prolongation is due to a cardiac pacemaker (and no other abnormalities in the heart), it is necessary to discuss with the sponsor's researcher to determine if the patient is suitable for group study; * patients suspected of having other primary cancers; * those who are known to be allergic to pharmaceutical ingredients. * patients with active or chronic hepatitis b (defined as having a positive hepatitis b surface antigen \[hbsag\] test at screening). patients with past/resolved hbv infection (defined as having negative hbsag test and a positive antibody to hepatitis b core antigen \[anti-hbc\] antibody test) are eligible. a negative hba dna test must be obtained in patients with positive hepatitis b core antibody prior to cycle 1 day 1. * active hepatitis c infection. patients positive hepatitis c antibody test are eligible if pcr is negative for hepatitis c viral dna. * pregnant or lactating women.