Apatinib for Advanced Osteosarcoma After Failure of Standard Multimodal Therapy

April 19, 2018 updated by: GUO WEI

A Phase II Trial of Apatinib in Relapsed and Unresectable High-grade Osteosarcoma After Failure of Standard Multimodal Therapy

After standard multimodal therapy, the prognosis of relapsed and unresectable high-grade osteosarcoma is dismal and unchanged over the last decades.Thus, the investigators explored apatinib activity in patients with relapsed and unresectable osteosarcoma after the failure of first-line or second-line chemotherapy. Patients >16 years, progressing after standard treatment, were eligible to receive 500 mg or 750 mg of apatinib once daily until progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) at 4 months and objective response rate (ORR). Secondary objectives were PFS, overall survival (OS), clinical benefit rate (CBR), defined as no progression at 6 months and safety.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients

Eligible patients should have the following characteristics: age >16 years; diagnosis of high-grade osteosarcoma confirmed histologically and reviewed centrally; prior treatment (completed >4 weeks before trial entry) consisted of standard high-grade osteosarcoma chemotherapy agents including doxorubicin, cisplatin, high-dose methotrexate, and ifosfamide; metastatic relapsed and unresectable progressive disease (PD); Eastern Cooperative Oncology Group performance status 0-1 with a life expectancy >3 months; adequate renal, hepatic, and hemopoietic function. Additionally, the investigators require normal or controlled blood pressure, as well as surgery and/or radiotherapy completion at least 1 month before enrollment. All enrolled patients showed radiological evidence of disease progression and the lesion could be evaluated according to RECIST 1.1 before treatment start.

Treatment

Patients are planned to be treated with a dose of apatinib 500 mg(BSA ≤1.5) or 750mg(BSA>1.5) once daily. The dose was reduced or temporarily suspended according to predefined rules and after considering any observed toxicity, which was assessed according to the Common Terminology Criteria for Adverse Events version 3.0. Following adverse event resolution, apatinib can be restarted at the maximally tolerated dose and continued until progression, unacceptable toxicity or patient refusal. The study was approved by participating hospital review boards, and conducted according to the Declaration of Helsinki and the International Conference on Harmonization of Good Clinical Practice guidelines. Each patient provided written informed consent.

Efficacy Assessment

Before starting treatment, patients should be staged with chest and abdomen computed tomography (CT) and magnetic resonance imaging (MRI) (whenever indicated by the clinical situation). And all those patients should be tested by Immunohistochemistry of the VEGFR-2 over-expression of the paraffin embedded samples of the lesion or mRNA testing VEGFR-2 over-expression of the fresh specimen. Baseline assessment included also full blood count, serum chemistry, electrocardiogram and physical examination. In light of its potential role in osteosarcoma response assessment, [18F]2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) is suggested but not mandated for patient enrollment, and its impact on tumor response assessment was purely exploratory. All tests were repeated after 2 months and, thereafter, at 2-month intervals unless there were toxic effects or disease progression suspicion. Response was assessed by CT/MRI scan according to RECIST 1.1. Thus, both complete and partial remission needed confirmation within 4 weeks of when a response was first demonstrated. Stable disease (SD) was confirmed after a minimum of 8 weeks. The investigators thoroughly probe for and record any sign(s) of treatment-induced improvement, be it minor response (MR) as tumor shrinkage <30%, and/or nondimensional tumor responses including Hounsfield unit measured tissue density changes or osteoid matrix calcification.

The primary end point progression-free survival (PFS) at 4 months is calculated from the date of treatment start until the time of disease progression or death, whichever came first. Patients alive and free from progression would be censored. Secondary end points included the following: PFS; OS; overall response rate, defined as complete responses (CRs) + partial responses (PRs) + MRs; disease control rate (overall response rate + SDs); patterns of nondimensional response; clinical benefit rate (CBR) (PFS rate at 4 months) and duration of response. Duration of response is calculated from the day of first response assessment until either progression/death (event) or last day of follow-up (censored). Last, the investigators evaluate any clinical improvement by means of the Pain Analgesic Score via the Brief Pain Inventory (BPI) score form that was filled in by patients themselves. Analgesic medication use was recorded according to the analgesic score: 0 = none; 1 = minor analgesics; 2 = tranquillizers, antidepressants, muscle relaxants and steroids; 3 = mild narcotics; 4 = strong narcotics.

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100044
        • Peking University People's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • age >16 years;
  • diagnosis confirmed histologically and reviewed centrally;
  • prior treatment (completed >4 weeks before trial entry) consisted of standard high-grade osteosarcoma chemotherapy agents including doxorubicin, cisplatin, high- dose methotrexate, and ifosfamide; metastatic relapsed and unresectable progressive disease (PD);
  • Eastern Cooperative Oncology Group performance status 0-1 with a life expectancy >3 months;
  • adequate renal, hepatic, and hemopoietic function;
  • normal or controlled blood pressure;
  • surgery and/or radiotherapy completion at least 1 month before enrollment.

Exclusion Criteria:

  • no pulmonary artery or venous tumor embolus;
  • previously exposed to other TKIs;
  • central nervous system metastasis;
  • have had other kinds of malignant tumors at the same time;
  • cardiac insufficiency or arrhythmia;
  • uncontrolled complications, such as diabetes mellitus and so on;
  • coagulation disorders;
  • urine protein≥ ++;
  • pleural or peritoneal effusion that needs to be handled by surgical treatment;
  • combined with other infections or wounds.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: apatinib
apatinib 750mg tablet or 500mg tablet by mouth, Qd half an hour after dinner
Drug: apatinib
Apatinib is a small-molecule VEGFR tyrosine kinase inhibitor, similar to vatalanib (PTK787), but with a binding affinity 10 times that of vatalanib or sorafenib.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival, PFS
Time Frame: 4 months
calculated from the date of treatment start until the time of disease progression or death, whichever comes first.
4 months
Objective response rate, ORR
Time Frame: 3 months
CR+PR at 3 months
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival, OS
Time Frame: 12 months
calculated from the date of treatment start until last follow-up or death, whichever comes first.
12 months
Clinical benefit rate, CBR
Time Frame: 6 months
CR+PR+SD at 6 months
6 months
Duration of response, DOR
Time Frame: 6 months
Duration of response is calculated from the day of first response assessment until either progression/death (event) or last day of follow-up (censored).
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

GUO WEI

Investigators

  • Study Chair: Wei Guo, M.D. Ph.D., Chinese Medical Association--Sarcoma group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2016

Primary Completion (Actual)

December 30, 2017

Study Completion (Actual)

January 8, 2018

Study Registration Dates

First Submitted

March 13, 2016

First Submitted That Met QC Criteria

March 16, 2016

First Posted (Estimate)

March 17, 2016

Study Record Updates

Last Update Posted (Actual)

April 23, 2018

Last Update Submitted That Met QC Criteria

April 19, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PKUPH-sarcoma

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

the investigator decide to share all the statistical analysis plan, clinical study report and anlytic code to other researchers

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Osteosarcoma

Clinical Trials on apatinib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cyprus

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe