Phase II Study for Combination of Camrelizumab and Apatinib in the Second-line Treatment of Recurrent or Metastatic Adrenocortical Carcinoma

Study Overview
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Brief Summary
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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.

Official Title
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Phase II Study for Combination of Camrelizumab and Apatinib in the Second-line Treatment of Recurrent or Metastatic Adrenocortical Carcinoma

Conditions
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Adrenocortical Carcinoma

Intervention / Treatment
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* Drug: Camrelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of adrenocortical carcinoma; 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); Aged >=18 years; Eastern Cooperative Oncology Group (ECOG) performance status 0-1; At least one measurable lesion, according to RECIST 1.1; 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) Appropriate contraception should be used from the start of treatment to 120 days after the end of treatment; Have signed consent form. Exclusion Criteria: 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; Have central nervous system metastasis with symptoms and need hormonal intervention; Had received strong CYP3A4 inhibitors within one week prior to enrollment or received strong CYP3A4 inducers within two weeks prior to enrollment; Poor control of high blood pressure (SBP>140mmHg or DBP>90mmHg); Congestive heart failure of New York Heart Association (NYHA) Class III or IV; Thromboembolic events occurred within 1 year prior to enrollment; ECG QT interval >500ms; Previous systemic immunosuppressive therapy; Previous anti-PD-1, anti-PD-L1 antibody or anti- CTLA-4 antibody treatment; Received TKI treatment within 2 weeks prior to starting the study drug; Participate in clinical trials of other interventional drugs within 4 weeks prior to starting the study drug; Received systemic therapy with corticosteroids or other immunosuppressants within 2 weeks prior to starting the study drug; An anti-tumor vaccine or a live vaccine was given within 4 weeks prior to starting the study drug; Major surgery or severe trauma within 4 weeks prior to starting the study drug; Severe infections occurred within 4 weeks prior to starting the study drug; Have an active autoimmune disease or a history of autoimmune diseases; Have a history of immunodeficiency; Have an active tuberculosis infection; Have active hepatitis; Patients with symptoms of gastrointestinal bleeding or risk of bleeding; Active infection, or patients are pregnant or breast-feeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Camrelizumab<br>* Camrelizumab was administered 200mg iv every 3 weeks, Apatinib was administered 250 mg p.o. qd.<br>* Other names: Apatinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | The rate of complete response and partial response. | up to 60 months |