Efficacy and Safety of Radiotherapy Combined With Apatinib Mesylate in the Treatment of Rhabdomyosarcoma in Children

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of radiotherapy combined with apatinib mesylate in the treatment of rhabdomyosarcoma in children.

Detailed Description
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This study is a Interventional study. The target group was 3-18 years old, and the pathological stage was group II-IV recurrence or distant metastasis. A total of 48 patients were enrolled in this study. The treatment was radiotherapy combined with apatinib. The main outcome measures were ORR, DCR , OS , quality of life and drug safety. The main safety indicators were vital signs, laboratory indicators, adverse events (AE), and severe adverse events (SAE). This study is expected to be enrolled for 6 months.

Official Title
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Efficacy and Safety of Radiotherapy Combined With Apatinib Mesylate in the Treatment of Rhabdomyosarcoma in Children

Conditions
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Childhood Rhabdomyosarcoma

Intervention / Treatment
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* Drug: Apatinib mesylate tablets
* Radiation: Three-dimensional conformal intensity modulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be ≥ 3 and ≤ 18 years of age. The predicted survival period is more than 3 months. According to RECIST version 1.1, there is at least one measurable lesion. Postoperative pathological stage was group II-IV. Patients have not received radiotherapy before, and can accept chemotherapy and surgical treatment. No other anticancer therapy should be used during radiotherapy. The main organs are functioning normally, which meets the following criteria: Blood routine examination standards should be met: (no blood transfusion within 14 days) A.HB>90g/L; B.ANC>1.5*109/L; C.PLT>80*109/L Biochemical tests should meet the following criteria: A. BIL < 1.25 times normal upper limit (ULN); B. ALT and AST < 2.5 ULN; C. Serum Cr < 1 ULN, endogenous creatinine clearance > 50 ml/min Subjects volunteered to participate in this study, patients or legal guardians signed informed consent through patient consent, good compliance, with follow-up. Doctors believe that treatment can benefit patients.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Simons two-stage design method requires the enrollment of 13 patients in the first stage. If more than 7 patients fail to reach the expected end point, the first stage fails and the patients do not need to enter the second stage. A total of 48 patients were enrolled. If more than 30 patients did not reach the expected end point, the overall trial failed.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiotherapy plus apatinib mesylate<br>All eligible patients signed informed consent. Three-dimensional conformal intensity modulation (IMRT) technique was used to treat the patients with radiation doses 45 Gy - 54 Gy. All patients took apatinib mesylate tablets 250 mg QD orally from 1 week before radiotherapy to the whole radiotherapy period. They were required to take apatinib mesylate tablets with warm boiling water half an hour after meal. The daily medication time should be as consistent as possible. | Drug: Apatinib mesylate tablets<br>* Apatinib mesylate tablets were orally administered 250 mg QD from 1 week before radiotherapy to the whole radiotherapy period. (Appatinib is no longer used after radiotherapy)<br>Radiation: Three-dimensional conformal intensity modulation<br>* Three-dimensional conformal intensity modulation (IMRT) technique was used for post-operative radiotherapy. The radiation dose was 45-54 Gy.<br>* Other names: 3D-IMRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Refers to the proportion of patients whose tumors have shrunk to a certain extent and maintained for a certain period of time, including CR and PR cases. Objective remission of solid tumors was assessed by RECIST 1.1. Subjects must be accompanied by measurable tumor lesions at baseline. According to RECIST 1.1, the criteria for evaluating efficacy are complete remission (CR), partial remission (PR), stability (SD), and progression (PD). | First analysis will occur 1 month after accrual of all patients. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | The percentage of patients whose tumors shrink or remain stable for a certain period of time | First analysis will occur 1 month after accrual of all patients. | 
| Total Survival (OS) | The time from enrollment to death for any reason. For those who had lost interviews before death, the last follow-up time was usually calculated as the time of death. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months. | 
| Quality of Life Score | Quality of life score refer to EORTC qlq-c30 (version 3, Chinese version). Quality of Life Questionnare-Core 30 prepared by The European O-rganization for Reasearch and Treatment of Cancer. EORTC qlq-c30 (V3.0) is the core scale for all cancer patients, with a total of 30 items. Items 29 and 30 are rated on a scale of 1 to 7 according to their answer choices. The other items are divided into four levels: totally not, a little bit, a lot and very much, and are scored on a scale of 1 to 4. The higher the score of functional domain and general health domain, the better the functional status and quality of life. The higher the score of symptom domain, the more symptoms or problems (the worse the quality of life). | Weekly assessment , assessed up to 1 month. | 
| Incidence and severity of Adverse Events | The safety of the drug was evaluated by NCI-CTCAE 4.0. Common Terminology Criteria Adverse Events Version 4.0 prepared by National Cancer Institute. | From date of enrollment until 30 days after the last medication. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiation Therapy, Rhabdomyosarcoma in Children