Phase II Study of PD-1 Inhibitor Combined With Apatinib and Mitotane in the Treatment of Advanced Adrenal Cortical Carcinoma
Adrenocortical carcinoma (ACC) is a rare aggressive malignant tumor. According to the literature, the 5-year survival rate of ACC is 12%-47%. For patients with advanced ACC, mitotane alone or combined with traditional chemotherapy was the first-line standard treatment, but its progression-free survival was only about 1 year. The efficacy of mitotane monotherapy is approximately 10% to 30%. FIRM-ACT trial reported an objective response rate (ORR) of 23.2% for etoposide, doxorubicin, cisplatin, and mitotane (EDP-M) chemotherapy regimen. Our phase II study found that PD-1 inhibitor camrelizumab and apatinib showed impressive clinical data in the second-line treatment of relapsed and metastatic ACC patients. The aim of this study is to evaluate the efficacy and safety of PD-1 inhibitor camrelizumab combined with apatinib and mitotane in advanced ACC, and to explore a new treatment strategy for patients with advanced ACC.
• Histopathological diagnosis of adrenocortical carcinoma;
• Patients with unresectable advanced adrenocortical carcinoma who have not received first-line standard treatment;
• Age ≥18 years old, ≤70 years old;
• No gender limit;
• Eastern Cooperative Oncology Group (ECOG) score 0-1;
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1);
• Major organ function within 28 days before treatment, meeting the following criteria:
• \- Blood routine test criteria (without blood transfusion within 14 days) : Hemoglobin (HB) ≥80g/L Absolute neutrophil count (ANC) ≥1.5×10\^9/L Platelet (PLT) ≥80×10\^9/L
• \- Biochemical tests must meet the following criteria: Total bilirubin (TBIL) ≤1.5 times the upper limit of normal value (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 ULN or ≤5 ULN if liver metastases are present Serum creatinine (Cr) ≤1.5 ULN or creatinine clearance (CCr)≥60 ml/min
• \- Coagulation testing requires the following criteria: International normalized ratio (INR) or prothrombin time (PT) ≤1.5 ULN Activated partial thromboplastin time (APTT) ≤1.5 ULN (if the patient is anticoagulated, as long as the PT and APTT are within the intended therapeutic range)
• \- Cardiac markers and natriuretic peptide (BNP) ≤ULN;
• Women of childbearing age should agree that they must use a contraceptive method (such as an intrauterine device, contraceptive pill, or condom) during the study and for 120 days after the study; Patients had a negative serum or urine pregnancy test within 7 days before study entry and had to be non-lactating; Men should consent to patients who must use contraception during the study and for 6 months after the end of the study period;
• Study participants provided written informed consent and were willing and able to follow planned visits, study treatments, laboratory tests, and other experimental procedures.