phase ii study for combination of camrelizumab and apatinib in the second-line treatment of recurrent or metastatic adrenocortical carcinoma

Conditions: Adrenocortical Carcinoma

Summary: 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. however, for patients who fail the first-line treatment, there is a lack of effective treatment. for acc patients who had failed first-line chemotherapy, a phase ii clinical trial found that the objective response rate and the disease control rate of pd-1 inhibitor keytruda were 14% and 64% respectively, and no grade 3 or 4 adverse events were observed. anti-tumor angiogenic drugs combined with pd-1 inhibitors have shown impressive clinical data in many solid tumors. this study is aimed to evaluate the efficacy and safety of pd-1 inhibitor camrelizumab combined with apatinib in patients with recurrent or metastatic acc after standard treatment failure, and to seek new treatment for this population.


Eligibility criteria:
inclusion criteria: 1. histologically confirmed diagnosis of adrenocortical carcinoma; 2. patients with metastatic or inoperable adrenocortical carcinoma that has progressed, metastasized, or recurred after first-line standard treatment (mitotane monotherapy, chemotherapy alone, mitotane combined chemotherapy); 3. aged \>=18 years; 4. eastern cooperative oncology group (ecog) performance status 0-1; 5. at least one measurable lesion, according to recist 1.1; 6. major organ functions within 28 days prior to treatment meet the following criteria(14 days without transfusion): hb≥80g/l, anc≥1.5x10\^9/l, plt ≥80x10\^9/l; tbil≤1.5 uln, alt and ast ≤2.5 uln, if there exists hepatic metastases, alt and ast ≤5 uln, cr ≤1.5 uln or ccr ≥60ml/min; inr or pt ≤1.5 uln, aptt ≤1.5 uln (if the patient is receiving anticoagulant therapy, pt and aptt should be within the expected treatment range); cardiac markers and bnp≤uln；tsh≤uln (if tsh is abnormal, t3 and t4 should be normal) 7. appropriate contraception should be used from the start of treatment to 120 days after the end of treatment; 8. have signed consent form. exclusion criteria: 1. patients with another primary malignancy within 5 years prior to starting the study drug, except for cured in situ cervical carcinoma and cured non-melanoma skin cancer; 2. have central nervous system metastasis with symptoms and need hormonal intervention; 3. had received strong cyp3a4 inhibitors within one week prior to enrollment or received strong cyp3a4 inducers within two weeks prior to enrollment; 4. poor control of high blood pressure (sbp\>140mmhg or dbp\>90mmhg); 5. congestive heart failure of new york heart association (nyha) class iii or iv; 6. thromboembolic events occurred within 1 year prior to enrollment; 7. ecg qt interval \>500ms; 8. previous systemic immunosuppressive therapy; 9. previous anti-pd-1, anti-pd-l1 antibody or anti- ctla-4 antibody treatment; 10. received tki treatment within 2 weeks prior to starting the study drug; 11. participate in clinical trials of other interventional drugs within 4 weeks prior to starting the study drug; 12. received systemic therapy with corticosteroids or other immunosuppressants within 2 weeks prior to starting the study drug; 13. an anti-tumor vaccine or a live vaccine was given within 4 weeks prior to starting the study drug; 14. major surgery or severe trauma within 4 weeks prior to starting the study drug; 15. severe infections occurred within 4 weeks prior to starting the study drug; 16. have an active autoimmune disease or a history of autoimmune diseases; 17. have a history of immunodeficiency; 18. have an active tuberculosis infection; 19. have active hepatitis; 20. patients with symptoms of gastrointestinal bleeding or risk of bleeding; 21. active infection, or patients are pregnant or breast-feeding.