A Study of Anlotinib Combined With or Without PD-1 Antibody on Unresectable High-grade Chondrosarcoma

NCT05193188 | Recruiting Phase 2

• 1 other identifier: LS2021-387
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

There is no standard treatment for chondrosarcoma. Some small sample of studies has shown that anti-angiogenic TKIs show certain activity in the treatment of chondrosarcoma. PD-1 inhibitors, in recent years, have also been used in clinical practice and showed good efficacy. We intend to explore the response of chondrosarcoma to PD-1 monoclonal antibody and the influence of different IDH genotypes on PD-1 monoclonal antibody response.

Conditions

Chondrosarcoma

Keywords

Chondrosarcoma Anlotinib PD-1 monoclonal antibody

Outcome Measures

Primary Outcomes (1)

• 6month-PFSR

  Proportion of no disease progression after 6 months of medication

  6month

Secondary Outcomes (2)

• ORR

  6month

• DCR

  6month

Study Arms (2)

Anlotinib combined with PD-1 monoclonal antibody

EXPERIMENTAL

Anlotinib, a multi-target tyrosine kinase inhibitor，oral，12mg/10mg/8mg，2 weeks on and 1 week off; PD-1 monoclonal antibody，PD-1 inhibitor，Intravenous injection，once 3 week.

Drug: Anlotinib hydrochloride; Drug: PD-1 inhibitor

Anlotinib monotherapy

ACTIVE COMPARATOR

Anlotinib, a multi-target tyrosine kinase inhibitor，oral，12mg/10mg/8mg，2 weeks on and 1 week off.

Drug: Anlotinib hydrochloride

Interventions

Anlotinib hydrochloride DRUG

Anlotinib 12mg per person per day, continuous medication for 2 weeks and 1 week off, 3 weeks 1 cycle, until disease progression or intolerable toxicity

Also known as: FuKeWei

Anlotinib combined with PD-1 monoclonal antibody; Anlotinib monotherapy

PD-1 inhibitor DRUG

Intravenous injection, once every 3 weeks, until the disease progression or intolerable toxicity

Anlotinib combined with PD-1 monoclonal antibody

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age ≥18 years old, no gender limit; 2. ECOG PS score 0-2 points; 3. unresectable locally advanced or metastatic chondrosarcoma confirmed by histopathology, including high-grade (grade II-III) conventional CS and dedifferentiated CS; 4. Allow previous surgery, radiotherapy, or chemotherapy therapies; 5. Have at least 1 measurable lesion in accordance with the RECIST1.1; 6. The main organs are functioning normally and meet the following criteria within 7 days before treatment:
• The standard of routine blood examination must be met (no blood transfusion and blood products within 14 days, no correction with G-CSF and other hematopoietic stimulating factors):
• Hemoglobin (HB) ≥90g/L;
• The absolute value of neutrophils (ANC) ≥ 1.5×109/L;
• Platelets (PLT) ≥100×109/L ② The biochemical inspection shall meet the following standards:
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• Total bilirubin (TBIL)≤1.5×upper limit of normal (ULN);
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN, if there is liver metastasis, ALT and AST ≤ 5×ULN;
• Serum creatinine (Cr)≤1.5×ULN or creatinine clearance (CCr)≥60ml/min;
• ③ Urine protein \<2+, and 24h urine protein quantitatively shows that the protein must be ≤ 1g;
• ④ Coagulation function: INR \<2.0 and APTT≤1.5×ULN
• ⑤ Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥ lower limit of normal value (60%)
• ⑥ Thyroid function: TSH ≤ upper limit of normal (ULN); if abnormal, T3 and T4 levels should be considered, and T3 and T4 levels are normal and can be included in the group; 9. The fertile male or female agrees to use reliable contraceptive methods during treatment and at least 12 months after the last study drug is taken; 10. Sign the informed consent form with my consent, have good compliance and cooperate with follow-up.

You may not qualify if:

• \. Received anti-CTLA-4/PD-1/PD-L1 antibody treatment previously ; 2. Received anti-angiogenic TKI drugs (such as Anlotinib, Apatinib, Regofenib, etc.) or anti-angiogenic antibody drugs (such as Bevacizumab) previously; 3. Received other anti-tumor treatments within 4 weeks before enrollment, including systemic therapy, radiotherapy, major surgery, open biopsy, or participated in other clinical trials; 4. Patients who have not recovered from adverse events caused by any previous treatment to NCI-CTCAE (5.0) ≤1, excluding hair loss; 5. The investigator determines that there is a significant risk of bleeding, including but not limited to:
• Imaging shows that the tumor has invaded important blood vessels or it is judged by the investigator that the tumor is likely to invade important blood vessels and cause fatal hemorrhage during the follow-up study, or accompanied by large veins (iliac blood vessels, inferior vena cava, pulmonary vein, superior vena cava) tumor thrombus formation, or a history of aneurysm and the possibility of rupture;
• Received major surgical operations or had obvious traumatic injuries within 4 weeks before enrollment, or had any bleeding or bleeding event ≥ NCI-CTCAE Grade 3, or had any unhealed wounds, ulcers or fractures;
• There is a tendency for hereditary or acquired bleeding and thrombosis, such as hemophilia patients, blood coagulation dysfunction, thrombocytopenia, hypersplenism, etc.;
• Abnormal coagulation function (INR\>1.5 or prothrombin time (PT)\>ULN+4 seconds or APTT\>1.5 ULN), have bleeding tendency, or are receiving thrombolytic or anticoagulant therapy;
• Patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or similar drugs; Note: Under the premise that the international normalized ratio of prothrombin time (INR) ≤ 1.5, the use of low-dose heparin (daily dosage for adults is 6,000 to 12,000 U) or low-dose aspirin (daily dosage ≤100 mg); 6. The following symptoms or comorbidities exist:
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• A history of hypertension, and can not be well controlled after treatment with 1-2 kinds of antihypertensive drugs (systolic blood pressure ≥150mmHg or diastolic blood pressure ≥100mmHg);
• Poorly controlled diabetes (fasting blood glucose\> 10mmol/L);
• Significant cardiovascular damage includes, but is not limited to: unstable angina, myocardial ischemia or myocardial infarction, grade ≥2 congestive heart failure (New York Heart Association (NYHA) classification); occurred within 6 months Arterial/venous thrombotic events, such as cerebrovascular accidents (including temporary ischemic attacks), deep vein thrombosis and pulmonary embolism;
• Sinus bradycardia of grade I or higher; or atrioventricular block of second degree or higher, or sinus arrest (except for pacemaker); arrhythmia (including QTc ≥480ms); need to take it at the same time to prolong the QTc interval Period drug
• Liver cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis require antiviral treatment;
• Urine routine test shows urine protein ≥ ++, and the 24-hour urine protein quantitative is confirmed to be\> 1.0 g;
• Renal failure requires hemodialysis or peritoneal dialysis;
• A history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation, hematopoietic stem cell transplantation, or receiving systemic corticosteroids within 2 weeks before enrollment Or any other form of immunosuppressive therapy; Note: In the absence of active autoimmune diseases, inhaled or topical steroids and adrenal corticosteroids with a dose of\> 10 mg/day prednisone equivalent dose are allowed, and the use of no more than 10 mg/day prednisone curative dose is allowed Adrenal corticosteroid replacement therapy, allowing glucocorticoids to be used as a preventive drug for hypersensitivity reactions (such as pre-docetaxel prophylaxis);

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

RECRUITING

Related Publications (1)

• Li B, Xie L, Liang J, Jiang Y, Wang K, Liu Y, Lin N, Huang X, Zhao K, Fan G, Liu M, Yan X, Qu H, Li H, Yang J, Zhou G, Ye Z. Anti-PD-1 antibody plus anlotinib vs. anlotinib alone in patients with refractory chondrosarcoma: A multicenter, non-randomized phase 2 FLAIL-C trial. Med. 2025 Nov 14;6(11):100809. doi: 10.1016/j.medj.2025.100809. Epub 2025 Aug 28.

  PMID: 40882625 DERIVED

MeSH Terms

Conditions

Chondrosarcoma

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Binghao Li, Medical PhD

  Second Affiliated Hospital of Zhejiang University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhaoming Ye, Medical PhD

CONTACT

86-0571-87783777; yezhaoming@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2021
• First Posted: January 14, 2022
• Study Start: February 6, 2023
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2026
• Last Updated: February 16, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)