Apatinib Plus IE Chemotherapy (Ifosfamide and Etoposide) for Relapsed or Refractory Osteosarcoma (AIEO)

Apatinib in Combination With Ifosfamide and Etoposide (IE) for Relapsed or Refractory Osteosarcoma Progressed Upon First-line Chemotherapy (AIEO): a Prospective, Multiple-centre, Single-arm, Phase 2 Trial

Apatinib has led to positive responses in the treatment of osteosarcoma refractory to first-line chemotherapy. However, apatinib demonstrates only short-lived activity, and the disease control of musculoskeletal lesions is worse than that of pulmonary lesions. This treatment failure has been partly overcome by the addition of ifosfamide and etoposide (IE). We have ever retrospectively compared the activity of apatinib + IE in relapsed or refractory osteosarcoma in two sarcoma centers in China and concluded that for osteosarcoma with multiple sites of metastasis, apatinib + IE demonstrated clinically meaningful antitumor activity and delayed disease progression in patients with recurrent or refractory osteosarcoma after failure of chemotherapy. However to overcome the influence of other interventions on the outcome, we are currently performing a prospective trial to investigate this combination, from which more accurate data on this treatment strategy are expected.

Study Overview

• Status: Recruiting
• Conditions: Effect of Drug; Toxicity, Drug
• Intervention / Treatment: Drug: apatinib

• Study Type: Interventional
• Enrollment (Anticipated): 44
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lu Xie, M.D.; Phone Number: +8613401044719; Email: xie.lu@hotmail.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University People's Hospital
      • Contact: Lu Xie, M.D.; Phone Number: +8613401044719; Email: xie.lu@hotmail.com
    • Beijing, Beijing, China, 100035
      • Active, not recruiting
      • Peking University Shougang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1) histologically confirmed high-grade osteosarcoma;
• 2) initial treatment in the Orthopedic/Oncology Departments of Peking University People's Hospital or Peking University Shougang Hospital;
• 3) progression less than 6 months after first-line chemotherapy with a combination of high-dose methotrexate, doxorubicin, cisplatin and ifosfamide (first-line chemotherapy);
• 4) measurable lesions according to the Response Evaluation Criteria for Solid Tumors (RECIST 1.1) ;
• 5) Eastern Cooperative Oncology Group performance status ≤ 2 ;
• 6) acceptable haematologic, hepatic, and renal function.

Exclusion Criteria:

• those who had been previously treated with antiangiogenic TKIs and single IE chemotherapy;
• those who had severe or uncontrolled medical disorders that could jeopardize the outcomes of the study. These confounding conditions included, cardiac clinical symptoms or disease with left ventricular ejection fraction<50%, and hypertension that could not be well controlled with antihypertensive drugs.;
• All patients were assessed by the sarcoma board including a thoracic surgeon with at least 10 years surgical experience. Patients with lung metastases only were carefully assessed for eligibility for metastasectomy, of whom those who were suitable for surgery were excluded from this study;
• weight loss of 20% or more before illness;
• brain or leptomeningeal metastasis;
• surgical procedure or radiotherapy within 4 weeks of enrollment;
• activegastroduodenal ulcer, previous condition associated with risk of bleeding or requiring anticoagulation;
• proteinuria or hematuria, denutrition with albuminemia <25 g/L;
• women who were pregnant or breast feeding, other malignancy;
• positive HBV/HCV/HIV serology, and known allergy to the experimental agents.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: apatinib+IE; Apatinib: 500 mg QD po (BSA ≥ 1.0) or 250 mg QD po (BSA < 1.0); IE: ifosfamide 1.8 g/m2/d d1-3; etoposide 100 mg/m2/d d1-3 Q2w	Drug: apatinib; Apatinib: 500 mg QD po (BSA ≥ 1.0) or 250 mg QD po (BSA < 1.0); IE: ifosfamide 1.8 g/m2/d d1-3; etoposide 100 mg/m2/d d1-3 Q2w; Other Names: IE chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	from the start of target treatment until disease progression or death, whichever came first.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	from the date of treatment initiation to death from any cause.	3 years

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Peking University Shougang Hospital; Jiangsu HengRui Medicine Co.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: March 27, 2021
• First Submitted That Met QC Criteria: March 27, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): July 16, 2021
• Last Update Submitted That Met QC Criteria: July 12, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: apatinib; osteosarcoma; advanced; etoposide; ifosfamide
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Osteosarcoma; Drug-Related Side Effects and Adverse Reactions; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: PKUPH-sarcoma 10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No