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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Rhabdomyosarcoma
• Intervention / Treatment: Drug: ATRA+VAC; Drug: ATRA+VAC+Anlotinib

• Study Type: Interventional
• Enrollment (Estimated): 106
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: xin Liu; Phone Number: 021-64175590-88503; Email: jeanettexin@hotmail.com

Study Locations

• China
  • Shanghai, China
    • Fudan University Cancer Hospital
    • Contact: xin Liu; Phone Number: 021-64175590-88503; Email: jeanettexin@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 14 years old and ≤ 60 years old;
2. Histologically confirmed medium to high risk rhabdomyosarcoma (excluding pleomorphic rhabdomyosarcoma);
3. The physical fitness status score of the Eastern Cancer Collaboration Group (ECOG) is 0-1;
4. Have not received any anti-tumor drug treatment in the past;
5. Expected survival time ≥ 3 months;

6. 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.

7. 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;
8. 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:

1. Previously received anti-tumor treatment other than surgery and radiation therapy for any malignant tumor;
2. Subjects who cannot accept or tolerate this chemotherapy regimen for various reasons;
3. Biopsy confirmed a patient with bone marrow infiltration;
4. 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;

5. 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)
6. Individuals with a known history of allergies to the components of this medication regimen;
7. The researcher believes that the patient is not suitable to participate in any other circumstances of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ATRA+VAC	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, orally, administered continuously every day, with 21 days constituting one course of treatment. If safety is confirmed, the dosage can be increased to 30mg bid.
Experimental: ATRA+VAC+Anlotinib	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 toxicity is intolerable, or for at least 2 years. All trans retinoic acid: provided free of charge by Shandong Liangfu Pharmaceutical Co., Ltd., capsule, 10mg/capsule, 20mg bid orally, administered continuously daily for 21 days as a course of treatment. If safety is ensured, the dosage will be increased to 30mg bid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
2-year event-free survival (EFS) rate	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)		up to 2 years
Objective response rate (ORR)		up to 2 years
Disease control rate (DCR)		up to 2 years
adverse event		up to 2 years
Quality of life (Functional Assessment of Cancer Therapy - General)		up to 2 years
The correlation between the gene status of PAX3/7-FOXO1 and therapeutic efficacy	Subgroup analysis of the effect of PAX3/7-FOXO1 gene expression on the 2-year EFS rate	up to 2 years

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: December 30, 2025
• First Submitted That Met QC Criteria: January 13, 2026
• First Posted (Actual): January 21, 2026

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Muscle Tissue; Myosarcoma; Rhabdomyosarcoma
• Other Study ID Numbers: RMS-ATRA-IIT-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No