Phase II Study of PD-1 Inhibitor Combined With Apatinib and Mitotane in the Treatment of Advanced Adrenal Cortical Carcinoma

June 1, 2025 updated by: Xingchen Peng, West China Hospital
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

28

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Recruiting
        • West China Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Histopathological diagnosis of adrenocortical carcinoma;
  2. Patients with unresectable advanced adrenocortical carcinoma who have not received first-line standard treatment;
  3. Age ≥18 years old, ≤70 years old;
  4. No gender limit;
  5. Eastern Cooperative Oncology Group (ECOG) score 0-1;
  6. At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1);

  7. 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;

  8. 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;
  9. Study participants provided written informed consent and were willing and able to follow planned visits, study treatments, laboratory tests, and other experimental procedures.

Exclusion Criteria:

  1. A history of other malignant tumors within the past 5 years or at the same time, except cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and thyroid papillary carcinoma;
  2. Known allergic reactions to other monoclonal antibodies, active ingredient of mitotane, active ingredient of apatinib and or any excipients;
  3. CNS metastases with clinical symptoms such as brain edema, requiring hormonal intervention, or progression of brain metastases;
  4. Patients who received potent CYP3A4 inhibitor treatment within one week before enrollment or a potent CYP3A4 inducer treatment within two weeks before the first use of study drug;
  5. Patients with hypertension not well controlled by antihypertensive drug therapy alone (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg);
  6. NYHA class III-IV congestive heart failure;
  7. Occurrence of arterial/venous thrombosis events within 1 year before enrollment, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), myocardial infarction, unstable angina pectoris, deep vein thrombosis, and pulmonary embolism;
  8. QT interval > 500 ms;
  9. Prior systemic immunosuppressive therapy;
  10. Prior treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies;
  11. TKI treatment within 2 weeks before the first dose;
  12. Participating in other interventional drug clinical trials within 4 weeks before the first dose;
  13. Received an antineoplastic vaccine or a live vaccine within 4 weeks before the first dose of study drug;
  14. Major surgery or major trauma within 4 weeks before the first dose of study medication;
  15. Had a serious infection (CTCAE > 2) within 4 weeks before the first dose of study drug, such as severe pneumonia requiring hospitalization, bacteremia, and infectious complications; The presence of active pulmonary inflammation, symptoms and signs of infection within 2 weeks before the first dose of the study drug, or the need for treatment with oral or intravenous antibiotics (excluding prophylactic antibiotics) on baseline chest imaging.
  16. Have an active autoimmune disease, a history of autoimmune disease (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases and syndromes); Autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone; Type 1 diabetes on stable doses of insulin; However, patients with vitiligo or childhood asthma/allergies that had been cured and did not need any intervention in adulthood were excluded.
  17. Have a history of immunodeficiency, including being HIV positive or having other acquired or congenital immunodeficiency disorders, or having a history of organ or bone marrow transplantation;
  18. A history of non-infectious pneumonia;
  19. Active pulmonary tuberculosis infection detected by medical history or CT examination, or a history of active pulmonary tuberculosis infection within 1 year before enrollment or patients who had a history of active pulmonary tuberculosis infection 1 year ago but had not received formal treatment;
  20. Subjects with active hepatitis (HBV DNA≥2000 IU/ml or 10000 copies/ml), hepatitis C (hepatitis C antibody positive and HCV-RNA above the detection limit of the assay);
  21. A known history of psychotropic drug abuse, alcohol abuse, and drug use;
  22. Have GI bleeding symptoms and risk of bleeding;
  23. Are pregnant or lactating;
  24. Have medical history, disease, treatment, or laboratory abnormalities that may interfere with the results of the trial or prevent the subject from participating fully in the study, or the investigator believes that participation in the study is not in the subject's best interest.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Camrelizumab in combination with apatinib and mitotane
Drug: Camrelizumab
Camrelizumab was administered 200mg IV every 3 weeks.
Drug: Apatinib
Apatinib was administered 250 mg PO QD.
Other Names:
  • YN968D1
  • Rivoceranib
Drug: mitotane
Mitotane is administered orally and plasma concentration was measured. The target steady-state plasma concentration is 14-20 mg/L.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
objective response rate
Time Frame: up to 24 months
The rate of complete response and partial response.
up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
disease-free survival
Time Frame: up to 60 months
The time from the administration of the first dose to first disease progression or death.
up to 60 months
progression-free survival
Time Frame: up to 60 months
The time from the commencement of therapy to the first evidence of disease progression or death.
up to 60 months
incidence of adverse events
Time Frame: up to 60 months
Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
up to 60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

West China Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 15, 2025

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2031

Study Registration Dates

First Submitted

February 13, 2025

First Submitted That Met QC Criteria

February 13, 2025

First Posted (Actual)

February 17, 2025

Study Record Updates

Last Update Posted (Actual)

June 3, 2025

Last Update Submitted That Met QC Criteria

June 1, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-1549

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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