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

Study Overview

• Status: Recruiting
• Conditions: Adrenocortical Carcinoma
• Intervention / Treatment: Drug: Camrelizumab

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xingchen Peng; Phone Number: +86 18980606753; Email: pxx2014@scu.edu.cn

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital, Sichuan University
      • Contact: Xingchen Peng; Phone Number: +86 18980606753; Email: pxx2014@scu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	Drug: Camrelizumab; Camrelizumab was administered 200mg iv every 3 weeks, Apatinib was administered 250 mg p.o. qd.; Other Names: Apatinib

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: West China Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Actual): December 1, 2023
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: March 20, 2020
• First Submitted That Met QC Criteria: March 20, 2020
• First Posted (Actual): March 24, 2020

Study Record Updates

• Last Update Posted (Actual): July 17, 2024
• Last Update Submitted That Met QC Criteria: July 16, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Adrenal Gland Diseases; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Adrenal Cortex Diseases; Carcinoma; Adrenocortical Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: ChiCTR1900028111

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No