Envafolimab Combined With Neoadjuvant Chemotherapy Treat Stage IIb Resectable Osteosarcoma Patients

Официальное название

Single-arm Prospective Clinical Study of PD-L1 Antibody Envafolimab Combined With Neoadjuvant Chemotherapy in Patients With Stage IIb Resectable Osteosarcoma

Обзор

Given that osteosarcoma typically presents at an early age and predominantly affects pediatric and adolescent populations, early control of disease progression and the opportunity for complete tumor resection are particularly crucial. Postoperatively, patients can regain functional mobility through prosthetic implantation and artificial joint reconstruction, thereby preventing premature loss of mobility in young patients. This study aims to explore the efficacy and safety of neoadjuvant treatment with the PD-L1 antibody envafolimab in combination with standard chemotherapy in patients with resectable stage IIb osteosarcoma, and to assess whether this combined regimen can increase the proportion of patients achieving complete tumor resection.

Вмешательства

• Препарат Envafolimab and neoadjuvant chemotherapy
  \* PD-L1 inhibitor envafolimab Paediatric (\<18 years): 2.5 mg/kg (maximum 200 mg) by subcutaneous injection on Day 1 of every week (q1w). Adult (≥18 years): 200 mg flat dose by subcutaneous injection on Day 1 of every week (q1w). * Neoadjuvant chemotherapy--MAP regimen (paediatric patients) Doxorubicin 75 mg/m² intravenously on Days 1-2, administered in weeks 1 and 6 of each 6-week cycle. Cisplatin 120 mg/m² intravenously on Days 1-3, administered in weeks 1 and 6 of each 6-week cycle. Meth

Первичные конечные точки

• Tumor necrosis rate [Срок оценки: From enrollment to the end of surgery, about 12th weeks.]

Вторичные конечные точки (4)

• EFS (event-free survival) [Срок оценки: About 1 year.]
• PFS (Progression-free survival) [Срок оценки: About 1 year.]
• Immune Microenvironment [Срок оценки: About 10th weeks after the start of neoadjuvant therapy (at definitive surgery).]
• Adverse Events (AEs) [Срок оценки: Adverse events (AEs) were recorded after enrollment and within 30 days of the last dose. Serious adverse events or adverse events related to the PD-L1 antibody envafolimab were extended to 90 days after the end of treatment.]

Критерии участия

Критерии включения

• Patients voluntarily participate in the study and have good compliance, signing a written informed consent form before enrollment.
• Age between 12 and 70 years, with no gender restrictions.
• Patients diagnosed with non-metastatic, resectable osteosarcoma by pathology and clinical physician assessment.
• Have measurable disease (according to RECIST 1.1 criteria, non-nodal lesions with a CT scan longest diameter ≥10 mm, and nodal lesions with a CT scan shortest diameter ≥15 mm).
• No prior systemic anti-tumor treatment.
• ECOG PS score: 0 to 1.
• Adequate organ function:

• Hematological parameters: Absolute Neutrophil Count (ANC) ≥1.5×10\^9/L, Platelet (PLT) ≥70×10\^9/L, Hemoglobin (HGB) ≥90 g/L.
• Hepatic function: Total Bilirubin (TBIL) ≤1.5×Upper Limit of Normal Value (ULN); Alanine Aminotransferase (ALT) and Aspartate Transferase (AST) ≤3×ULN; Serum Albumin ≥28 g/L; Alkaline Phosphatase (ALP) ≤5×ULN; patients on routine hepatic protection treatment meeting the above criteria and stable for at least one week after investigator assessment may be included.
• Renal function: Creatinine (Cr) ≤1.5×ULN, or Creatinine clearance rate ≥50 mL/min (using the standard Cockcroft-Gault formula).
• Coagulation function: International Normalized Ratio (INR) ≤1.5, Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN; if the subject is undergoing anticoagulant therapy, PT and INR within the intended range of the anticoagulant therapy is acceptable.

Критерии исключения

• Participants with a history of or concurrent diagnosis of other malignant tumors (except for cured cutaneous basal cell carcinoma and in situ cervical carcinoma).
• Patients with recurrent postoperative or previously treated osteosarcoma with local or systemic anti-tumor therapy, or with metastasis.
• Participants who have received the following treatments within 4 weeks prior to study initiation: radiation therapy for tumors, surgical procedures, chemotherapy, immunotherapy, or other investigational drugs.
• Known allergies to any component of the study medication in participants. Participants with uncontrolled clinical symptoms or diseases of the heart, such as: (1) NYHA Class II or higher heart failure, (2) unstable angina pectoris, (3) myocardial infarction within the past year, (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
• Participants with active infections or fever of unknown origin >38.5°C (measured in Celsius) during the screening period or before the first dose of study medication (fever due to tumors may be included at the discretion of the investigator).
• Use of immunosuppressive drugs within 14 days prior to treatment initiation, excluding intranasal and inhaled corticosteroids or physiological doses of systemic corticosteroids (i.e., daily dose of prednisone ≤10 mg or equivalent physiological doses of other corticosteroids).
• History of active autoimmune diseases or a history of autoimmune disorders (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary glanditis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; participants with vitiligo or asthma that may be in complete remission in childhood and currently do not require medical intervention, or history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation).
• Participants who have received live vaccines within 4 weeks prior to study medication or are likely to receive live vaccines during the study period.
• Participants with a history of substance abuse, alcoholism, or drug addiction.
• Participants deemed to be excluded from this study by the investigator, such as those with other factors that could potentially lead to premature termination of the study, such as other serious diseases (including psychiatric diseases) requiring concomitant treatment, severe laboratory abnormalities, or family or social factors that could affect participant safety, or collection of data and samples.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shanghai First People's Hospital, 100 Haining Road, Hongkou District — Шанхай

Идентификаторы

NCT: NCT07142863 · 2024SQ009

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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