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

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

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.

Study Overview

• Status: Completed
• Conditions: Efficacy; Toxicity
• Intervention / Treatment: Drug: Methylsulfonic apatinib

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100044
    • Musculoskeletal Tumor Center of Peking University People's Hospital
  • Beijing, China, 100144
    • Peking University Shougang Hospital

Participation Criteria

Eligibility Criteria

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

Description

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.

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: osteosarcoma; all patients had been given apatinib alone	Drug: Methylsulfonic apatinib; Anti-angiogenesis Tyrosine kinase inhibitor which specifically inhibits VEGFR-2.
Experimental: Ewing sarcoma; Some of patients had been given apatinib alone while some of them had been given apatinib+everolimus	Drug: Methylsulfonic apatinib; Anti-angiogenesis Tyrosine kinase inhibitor which specifically inhibits VEGFR-2.
Experimental: soft tissue sarcoma; 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; Anti-angiogenesis Tyrosine kinase inhibitor which specifically inhibits VEGFR-2.
Experimental: Chondrosarcoma; Patients were given apatinib alone	Drug: Methylsulfonic apatinib; Anti-angiogenesis Tyrosine kinase inhibitor which specifically inhibits VEGFR-2.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Peking University Shougang Hospital; Peking University International Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): December 31, 2016
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: March 31, 2018
• First Submitted That Met QC Criteria: March 31, 2018
• First Posted (Actual): April 9, 2018

Study Record Updates

• Last Update Posted (Actual): April 10, 2018
• Last Update Submitted That Met QC Criteria: April 6, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: apatinib; tyrosine-kinase inhibitors; osteosarcoma; Ewing sarcoma; chondrosarcoma; soft-tissue sarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: PKUPH-sarcoma 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
• product manufactured in and exported from the U.S.: No