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This is a randomized controlled phase II clinical study aimed at evaluating the efficacy and safety of anlotinib hydrochloride in children with Intermediate-High -risk rhabdomyosarcoma. The study enrolled children with rhabdomyosarcoma confirmed by histopathology, with a clinical risk classification of high or Intermediate-risk accompanied by high-risk factors (high-risk factors are defined as age > 10 years,Poor prognosis molecular characteristics or those who cannot undergo surgery/radiotherapy);One year of maintenance treatment with anlotinib can increase the duration of response and long-term survival.
Anlotinib Hydrochloride is a novel multi-target tyrosine kinase inhibitor.It can effectively inhibit kinases such as VEGFR, PDGFR, FGFR, c-Kit and Met, and has the functions of anti-tumor angiogenesis and inhibiting tumor growth.Especially for vascular endothelial growth factor receptor 2 (VEGFR2/KDR) and VEGFR3 shows a highly selective inhibitory effect, with a half-maximal inhibitory concentration (IC50) of less than 1.0 nM, which is significant, and has a significant anti-angiogenic effect.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Combination medication group | Experimental |
| |
| Conventional maintenance treatment | Active Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Anlotinib+Cyclophosphamide+Vinorelbine | Drug | Anlotinib hydrochloride capsules combined with Cyclophosphamide+Vinorelbine), Anlotinib hydrochloride capsules 8mg (weight ≤35kg) or 12mg (weight > 35kg), po, qd, D1-D14;on an empty stomach ,Two weeks off for one week,with a cycle of 3 weeks. Cyclophosphamide 25mg/m2, po, qd, D1-D28, with a cycle of 4 weeks. vinorelbine 60g/m2, po, qw, D1, 8,15, with a cycle of 4 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| DOR (Duration of Response) | DOR (Duration of Response) refers to the period from the first assessment of complete response (CR) or partial response (PR) of the tumor to the first assessment of disease progression (PD) or death from any cause. | 2 year |
| Measure | Description | Time Frame |
|---|---|---|
| 2-year DFS rate | The 2-year DFS rate refers to the probability that a patient does not experience disease recurrence or progression within 2 years after cancer treatment. | 2 year after treatment |
| 2-year OS rate |
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Inclusion Criteria:1.Age ≥5 years old, ≤18 years old, no gender restrictions; 2.ECOG performance status (PS) 0-3 points; 3.The expected survival period is not less than 12 weeks; 4.with high-risk or intermediate-risk rhabdomyosarcoma with high-risk factors (high-risk factors are defined as age > 10 years, poor prognostic molecular features, or inoperable/radiotherapy-ineligible) confirmed by histopathology ; 5.Complete remission was achieved after first-line treatment. 6.Patients must have fully recovered from the acute toxic effects of all prior anticancer chemotherapy: 7.Myelosuppressive chemotherapy: at least 21 days after the last myelosuppressive chemotherapy (42 days if nitrosoureas were used previously); 8.Investigational drugs or anticancer therapies other than chemotherapy: should not be used within the first 28 days of the planned start of anlotinib . Patients must have fully recovered from clinically significant toxicity of the therapy; 9.Hematopoietic growth factors: at least 14 days after the last dose of long-acting growth factors or 3 days after the last dose of short-acting growth factors; 10.Immunotherapy: at least 14 days after completing any type of immunotherapy (except steroids), such as immune checkpoint inhibitors and tumor vaccines; 11.X-ray therapy (XRT): at least 14 days after local palliative XRT (small-scale oral); if other parenchymal bone marrow (BM) irradiation is performed, including previous radioiodinated metaiodobenzylguanidine (131I-MIBG) treatment, it must be completed at least 42 days; 12.Stem cell infusion without total body irradiation (TBI): No evidence of active graft-versus-host disease, and the patient must have completed at least 56 days after transplantation or stem cell infusion; 13.Laboratory tests during the screening period should meet the following conditions: Absolute neutrophil count ( ANC) ≥ 1.5 × 109/L (ANC ≥ 1.0 × 109/L if bone marrow involvement occurs) Platelet count ( PLT) ≥75 × 109/L (PLT ≥50 × 109/L if bone marrow involvement occurs) Bilirubin ≤ 1.5 times ULN Creatinine ≤ 1.5 times ULN (calculated according to the standard Cockcroft-Gault formula) ALT/AST ≤ 3 times ULN (can be relaxed to 5 times ULN if liver metastasis is present) 14.Ability to comply with outpatient treatment, laboratory monitoring, and necessary clinical visits during study participation; 15.The parent/guardian of the child or adolescent subject is capable of understanding, agreeing to, and signing the Informed Consent Form (ICF) and applicable Child Assent Form before initiating any protocol-related procedures; and the subject is capable of expressing consent (where applicable) with the consent of the parent/guardian.
Exclusion Criteria:Patients with any of the following cannot be enrolled in this study :
HBsAg positive and HBV DNA above the upper limit of normal Anti-HCV positive and HCV RNA positive HIV positive
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| yizhuo zhang | Contact | 0086-18819241079 | zhangyzh@sysucc.org.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sun Yat-sen University Cancer Center | Guangzhou | Gongdong | 510060 | China |
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| Cyclophosphamide+Vinorelbine | Drug | Cyclophosphamide 25mg/m2, po, qd, D1-D28, with a cycle of 4 weeks. vinorelbine 60mg/m2, po, qw, D1, 8,15, with a cycle of 4 weeks. |
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2-year OS rate is defined as the percentage of patients who do not experience death from any cause after 2-year treatment.
| 2 year after treatment |
| Adverse events (AE) | An AE refers to any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, but which does not necessarily have a causal relationship with this treatment. Number and classification of participants with treatment-related adverse events as assessed by CTCAE v5.0 were recorded. | 2 year |