A Clinical Study on the Efficacy and Safety of All-trans Retinoic Acid Combined With VAC Regimen in the Treatment of Intermediate-to-high-risk Rhabdomyosarcoma

Официальное название

A Multicenter, Multi-cohort, Prospective Phase II Clinical Study on the Efficacy and Safety of All-trans Retinoic Acid Combined With VAC Regimen in the Treatment of Intermediate-to-high-risk Rhabdomyosarcoma

Обзор

This study is a prospective, multi-cohort, multi-center clinical trial targeting patients with intermediate-to-high-risk rhabdomyosarcoma who have not previously received systemic anti-tumor treatment. It aims to evaluate the efficacy and safety of all-trans retinoic acid combined with VAC chemotherapy.

Вмешательства

• Препарат ATRA+VAC
  Cohort 1: Intermediate-risk RMS: ATRA+VAC treatment The specific medication is: Vincristine (V), administered intravenously, at a dose of 1.5 mg/m2 (with a maximum of 2 mg), on days 1, 8, and 15, every three weeks. Dactinomycin (A), intravenous infusion, 1.25mg/m2 (maximum not exceeding 2.5mg), D1, q3w. Cyclophosphamide (C), intravenous infusion, 1200mg/m2, D1, q3w. All-trans-retinoic acid: provided free of charge by Shandong Liangfu Pharmaceutical Co., Ltd. Capsules, 10mg/capsule, 20mg bid,
• Препарат ATRA+VAC+Anlotinib
  Cohort 2: High risk group RMS+: ATRA+VAC, ATRA+anlotinib maintenance therapy The specific medication is: Vincristine (V), static push, 1.5 mg/m2 (maximum not exceeding 2mg), D1, 8, 15, q3w. Dactinomycin (A), intravenous drip, 1.25mg/m2 (maximum not exceeding 2.5mg), D1, q3w. Cyclophosphamide (C), intravenous infusion, 1200mg/m2, D1, q3w. After chemotherapy, Anlotinib, 12mg, d1-d14, po, q3w+ATRA maintenance therapy. Both are maintained for a period of time until disease progression or toxicit

Первичные конечные точки

• 2-year event-free survival (EFS) rate [Срок оценки: up to 2 years]

Вторичные конечные точки (6)

• Overall survival (OS) [Срок оценки: up to 2 years]
• Disease control rate (DCR) [Срок оценки: up to 2 years]
• Objective response rate (ORR) [Срок оценки: up to 2 years]
• adverse event [Срок оценки: up to 2 years]
• Quality of life (Functional Assessment of Cancer Therapy - General) [Срок оценки: up to 2 years]
• The correlation between the gene status of PAX3/7-FOXO1 and therapeutic efficacy [Срок оценки: up to 2 years]

Критерии участия

Критерии включения

• Age ≥ 14 years old and ≤ 60 years old;
• Histologically confirmed medium to high risk rhabdomyosarcoma (excluding pleomorphic rhabdomyosarcoma);
• The physical fitness status score of the Eastern Cancer Collaboration Group (ECOG) is 0-1;
• Have not received any anti-tumor drug treatment in the past;
• Expected survival time ≥ 3 months;
• Possess sufficient organ and bone marrow function, with laboratory test values meeting the following requirements within 7 days prior to enrollment (no blood components, cell growth factors, albumin, or other corrective treatment drugs are allowed within 14 days prior to obtaining laboratory tests), as follows Blood routine: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count (PLT) ≥ 100 × 109/L, hemoglobin (HGB) ≥ 100 g/L (no transfusion or erythropoietin dependence within 14 days) Liver function: serum total bilirubin ≤ 1.25 times the upper limit of normal (ULN); ALT and AST ≤ 2.5 x ULN (≤ 5x ULN for patients with liver metastases); Serum albumin ≥ 30 g/L; Alkaline phosphatase (ALP) ≤ 5 × ULN.

Renal function: Serum creatinine (Cr) ≤ 1.25 × ULN, or creatinine clearance rate ≥ 60 mL/min (using the standard Cockcroft Gault formula): Urine routine results show urinary protein<2+; For patients whose baseline urine routine test shows urinary protein ≥ 2+, 24-hour urine collection should be performed with a 24-hour urine protein quantification of<1g.

Coagulation function: International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; If the subject is receiving anticoagulant therapy, as long as the INR is within the intended range of use of the anticoagulant drug.

• For female subjects of childbearing age, a urine or serum pregnancy test should be conducted 3 days before receiving the first study drug and the result should be negative;
• Participants and their sexual partners are required to use a medically approved contraceptive measure (such as intrauterine devices, birth control pills, or condoms) during the study treatment period and within 6 months after the end of the study treatment period.

Критерии исключения

• Previously received anti-tumor treatment other than surgery and radiation therapy for any malignant tumor;
• Subjects who cannot accept or tolerate this chemotherapy regimen for various reasons;
• Biopsy confirmed a patient with bone marrow infiltration;
• Patients who have undergone major surgical procedures unrelated to medium to high risk rhabdomyosarcoma within the 4 weeks prior to enrollment, or who have not fully recovered from such surgical procedures;
• Serious heart disease or discomfort, including but not limited to the following diseases:

• Diagnosed history of heart failure or systolic dysfunction (LVEF<50%);
• High risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate>100bpm, significant ventricular arrhythmias (such as ventricular tachycardia), or higher-level atrioventricular block (i.e. Mobitz II second or third degree atrioventricular block);
• Angina requiring treatment with anti angina drugs;
• Clinically significant heart valve disease;
• ECG shows transmural myocardial infarction;
• Poor control of hypertension (systolic blood pressure>180mmHg and/or diastolic blood pressure>100mmHg)
• Individuals with a known history of allergies to the components of this medication regimen;
• The researcher believes that the patient is not suitable to participate in any other circumstances of this study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Fudan university cancer hospital — Шанхай

Идентификаторы

NCT: NCT07355855 · RMS-ATRA-IIT-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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