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

Official title

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

Overview

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.

Interventions

• Drug 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,
• Drug 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

Primary outcome measures

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

Secondary outcome measures (6)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan university cancer hospital — Shanghai

Identifiers

NCT: NCT07355855 · RMS-ATRA-IIT-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗