Apatinib for Advanced Sarcoma: Results From Multiple Institutions' Off-label Use

Study Overview
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Brief Summary
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Anti-angiogenesis Tyrosine kinase inhibitors (TKIs) have been proved to show promising effects on prolonging progression-free survival (PFS) for advanced sarcoma after failure of standard multimodal Therapy. Methylsulfonic apatinib is one of those TKIs which specifically inhibits VEGFR-2. This study summarizes the experience of three Peking University affiliated hospitals in off-label use of apatinib in the treatment of extensively pre-treated sarcoma.

Detailed Description
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The investigators retrospectively analysed files of patients with advanced sarcoma not amenable to curative treatment, who were receiving an apatinib-containing regimen between June 1, 2015 and December 1, 2016. Fifty-six patients were included: 22 osteosarcoma, 10 Ewing's sarcoma, 3 chondrosarcoma and 21 soft tissue sarcoma.

Official Title
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The Effectivity and Toxicity of Methylsulfonic Apatinib for Extensively Pre-treated Advanced Sarcoma: a Multicentric Retrospective Study in China

Conditions
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Efficacy, Toxicity

Intervention / Treatment
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* Drug: Methylsulfonic apatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) histologically confirmed high-grade sarcoma; 2) initial treatment in the orthopedic oncology departments of the three affiliated hospitals of Peking University; 3) tumors not amenable to curative treatment or inclusion in clinical trials; 4) unresectable local advanced lesions or multiple metastatic lesions that could not be cured by local therapy; 5) measurable lesions according to Response Evaluation Criteria for Solid Tumors (RECIST1.1) [8]; 6) Eastern Cooperative Oncology Group performance status 0 or 1 [9]; and 7) acceptable hematologic, hepatic, and renal function. Exclusion Criteria: had been previously exposed to other TKIs; had central nervous system metastasis; had other kinds of malignant tumors at the same time; had cardiac insufficiency or arrhythmia; had uncontrolled complications such as diabetes mellitus, coagulation disorders, urine protein ≥ ++ and so on; had pleural or peritoneal effusion that needs to be handled by surgical treatment; combined with other infections or wounds were pregnant or breastfeeding.
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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: osteosarcoma<br>all patients had been given apatinib alone | Drug: Methylsulfonic apatinib<br>* Anti-angiogenesis Tyrosine kinase inhibitor which specifically inhibits VEGFR-2.<br>|
| Experimental: Ewing sarcoma<br>Some of patients had been given apatinib alone while some of them had been given apatinib+everolimus | Drug: Methylsulfonic apatinib<br>* Anti-angiogenesis Tyrosine kinase inhibitor which specifically inhibits VEGFR-2.<br>|
| Experimental: soft tissue sarcoma<br>Some of the patients had been given apatinib alone while some of the patients had been given apatinib together with GT chemotherapy, which was gemcitabine 1000 mg/m2 d1,8 and docetaxel 75 mg/m2 d8 once every 21 day. | Drug: Methylsulfonic apatinib<br>* Anti-angiogenesis Tyrosine kinase inhibitor which specifically inhibits VEGFR-2.<br>|
| Experimental: Chondrosarcoma<br>Patients were given apatinib alone | Drug: Methylsulfonic apatinib<br>* Anti-angiogenesis Tyrosine kinase inhibitor which specifically inhibits VEGFR-2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | CR+PR accroding to RECIST 1.1 | 3 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival, PFS | PFS was defined as time from the start of using apatinib until disease progression or death, whichever occurred first. | 4 months and 6 months | 
| duration of response, DOR | The time from appearance of response or stable disease to progression or death was thus considered the DOR | 4 months | 
| Overall Survival,OS | OS was defined as time from the start of using apatinib until death. | 12 months | 
| toxicity | accroding to the Common Terminology Criteria for Adverse Events 4.0 | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ewing sarcoma, apatinib, tyrosine-kinase inhibitors, osteosarcoma, chondrosarcoma, soft-tissue sarcoma