Apatinib Combined With Camrelizumab in Treating Participants With Advanced Chordoma

NCT ID: NCT06140732

Last Updated: 2023-11-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-30
• Study Completion Date: 2026-01-31

Brief Summary

This phase II trial studies how well Camrelizumab combined with Apatinib work in treating participants with chordoma that has spread to other places in the body, which may interfere with the ability of tumor cells to grow and spread.

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the clinical benefit of the combination of Camrelizumab combined with Apatinib in patients with advanced chordomas by adverse events (AEs) and progression free survival (PFS).

SECONDARY OBJECTIVES:

I. Ascertain the safety of nivolumab in combination with relatlimab in subjects with metastatic or locally advanced/unresectable chordoma by the Overall survival (OS), objective response rate (MPR) and disease control rate (DCR)

EXPLORATORY OBJECTIVES:

I. Compare response rate (RR) and clinical benefit rate (CBR) in patients whose tumors are PD-L1+ and PD-L1- at baseline.

II. Compare RR and CBR in patients whose tumors are VEGFR+ and VEGFR- at baseline.

III. In the patients who are PD-L1 positive, compare RR and CBR in patients with 1% and 5% tumor membrane staining.

III. Determine the response to treatment based on the baseline mutation load. IV. Determine the ORR and CBR via Choi criteria.

OUTLINE:

To evaluate the safety and tolerability of carrilizol combined with apatinib in patients with recurrent, unresectable, chemotherapy-failed chordoma

After completion of study treatment, participants are followed up within 3 months.

Conditions

Chordoma; Chemotherapy Effect

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

camrelizumab combined with apatinib

camrelizumab 200 mg iv/ q2w+ apatinib 375mg oral qd

Group Type: EXPERIMENTAL

camrelizumab and apatinib

Intervention Type: DRUG

camrelizumab 200 mg iv/ q2w+ apatinib 375mg oral qd

Interventions

camrelizumab and apatinib

camrelizumab 200 mg iv/ q2w+ apatinib 375mg oral qd

Intervention Type: DRUG

Other Intervention Names

Targeted therapy

Eligibility Criteria

Exclusion Criteria

1. The standard of blood routine examination should be met (no blood transfusion and blood products within 14 days, no G-CSF and other hematopoietic stimulating factors are used to correct) :

1. Hemoglobin (Hb) ≥ 80 g/L;

2. Neutrophil count (ANC) ≥ 1.5×109/L;

3. Platelet count (PLT) ≥ 80×109/L;

2. Biochemical examination shall meet the following standards:

1. Total bilirubin (TBIL) < 1.5 ULN;

2. ALT and AST < 2.5ULN, and < 5ULN in patients with liver metastasis; Alkaline phosphatase < 5ULN;

3. Serum Cr ≤ ULN or endogenous creatinine clearance > 45 ml/min. 8. Women of childbearing age must have used reliable contraception or had a pregnancy test (serum or urine) within 7 days prior to enrol, with a negative result, and be willing to use an appropriate method of contraception during the trial period and 60 days after the last dose of the test drug. For men, consent to use appropriate methods of contraception or surgical sterilization during the trial period and for 120 days after the last dose of the trial drug; 9. The subjects voluntarily joined the study and signed the informed consent, with good compliance and follow-up.

1. Except for those subjects whose toxicity had not recovered from previous antitumor therapy (concurrent chemoradiotherapy, surgical treatment) (alopecia, alkaline phosphatase, glutamine detranspeptase (GGT)) or who could be enrolled after discussion with the investigator and sponsor

2. Use of immunosuppressive drugs within 14 days prior to first use of carrilizumab, excluding nasal and inhaled corticosteroids or systemic steroid hormones at physiological doses (i.e., no more than 10 mg/ day of prednisolone or other corticosteroids at pharmacologically equivalent doses);

3. Previous treatment with anti-PD-1, anti-PD-L1, anti-VEGFR antibodies or anti-PD-L2 drugs or drugs that target another stimulus or synergistically inhibit T cell receptors (e.g., CTLA-4, OX-40, CD137);

4. Uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 90 mmHg, despite systematic medication);

5. Severe cardiovascular disease: Grade II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc interval ≥450 ms for men and ≥470 ms for women); Grade Ⅲ to Ⅳ cardiac insufficiency (according to the New York Heart Society NYHA classification, see Annex 3), or left ventricular ejection fraction (LVEF) < 50% indicated by cardiac color ultrasound;

6. Patients with any active autoimmune disease or history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism) are not included;

7. The subjects were treated with bronchodilators and other systemic treatments, but their asthma control was unsatisfactory and they could not be included (those whose asthma had been completely relieved in childhood could be included without any intervention after adulthood).

8. Urine routine suggests urinary protein ≥ ++, or confirms 24-hour urinary protein volume ≥1.0g;

9. Abnormal coagulation function (INR >1.5 ULN or prothrombin time (PT) > ULN+4 seconds or APTT >1.5 ULN), have a tendency to bleed or are receiving thrombolytic or anticoagulant therapy; Note: Under the premise of INR ≤ 1.5, the use of low dose heparin (adult daily dose of 0.6 thousand to 12 thousand U) or low dose aspirin (daily dose of 100 mg or less) is permitted for preventive purposes;

10. A severe infection occurring within 4 weeks prior to the first dose (e.g., requiring intravenous antibiotic, antifungal, or antiviral medication), or an unexplained fever >38.5°C during the screening period/prior to the first dose;

11. Severe arteriovenous thrombosis events, such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, occurred within 12 months before enrollment;

12. Had undergone major surgery or severe traumatic injury, fracture or ulcer within 4 weeks prior to enrollment;

13. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), active tuberculosis, active hepatitis B (HBV DNA ≥ 500 IU/ml), hepatitis C (hepatitis C antibody positive, And HCV-RNA is higher than the lower limit of detection method) or co-infected with hepatitis B and hepatitis C;

14. Patients with a clear history of allergy may have an underlying allergy or intolerance to the biologics of Apatinib and carrilizumab;

15. There are significant factors affecting the absorption of oral drugs, such as inability to swallow, chronic diarrhoea and intestinal obstruction. Or have cavity or perforation of viscera or sinus within 6 months;

16. Those who have a history of psychotropic drug abuse and cannot quit or have mental disorders;

17. Increases the risks associated with study participation or study drugs and, in the investigator's judgment, may result in other conditions for which the patient is not eligible for study enrollment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Xuanwu Hospital, Beijing

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zan Chen

Role: PRINCIPAL_INVESTIGATOR

Xuanwu Hospital, Beijing

Locations

BEIJING

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zan Chen, Dr.

Role: CONTACT

qimaoyang777@163.com

18131166269

Zan Chen

Role: CONTACT

chenzan66@163.com

+861391171212

Facility Contacts

Zan Chen, MD

Role: primary

13911712120@163.COM

13911712120 ext. +86

References

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Reference Type: BACKGROUND

PMID: 35934010 (View on PubMed)

Liu C, Jia Q, Wei H, Yang X, Liu T, Zhao J, Ling Y, Wang C, Yu H, Li Z, Jiao J, Wu Z, Yang C, Xiao J. Apatinib in patients with advanced chordoma: a single-arm, single-centre, phase 2 study. Lancet Oncol. 2020 Sep;21(9):1244-1252. doi: 10.1016/S1470-2045(20)30466-6.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Ulici V, Hart J. Chordoma. Arch Pathol Lab Med. 2022 Mar 1;146(3):386-395. doi: 10.5858/arpa.2020-0258-RA.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: RESULT

PMID: 37429302 (View on PubMed)

Other Identifiers

XW-NS-ACCFC

Identifier Type: -

Identifier Source: org_study_id