Apatinib + Ifosfamide and Etoposide for Relapsed or Refractory Osteosarcoma

Apatinib+Ifosfamide and Etoposide (IE) Versus IE Alone for Relapsed or Refractory Osteosarcoma: a Real-world Study in Two Centers in China

Today, using a multi-modal approach consisting of preoperative (neoadjuvant) systemic polychemotherapy followed by local surgical therapy and then postoperative (adjuvant) chemotherapy, long-term, disease-free survival can be achieved in 60- 70% of osteosarcoma patients. However treatment options for osteosarcomas, especially in the setting of metastatic or unresectable disease, are very scarce. Apatinib has been proved to be an effective agent to prolong progression-free survival in advanced osteosarcoma. But after 4-6 months' treatment, secondary resistance always occurred with musculoskeletal lesions' progression or new metastasis.

Nowadays giving therapeutic doses of IE concurrently with anti-angiogenesis tyrosine kinase inhibitors is a conceptually attractive strategy for treating patients with refractory osteosarcoma according to prospective trial of lenvatinib +IE reported by Gaspar et al at 2019 ESMO and 2020 ESMO. Thus This study was designed to review our experience in real world for off-label use and characterize the toxicity profile of concurrent apatinib+IE and IE alone in patients with relapsed or refractory osteosarcoma.

Study Overview

• Status: Completed
• Conditions: Effect of Drug; Toxicity, Drug; Secondary Resistance
• Intervention / Treatment: Drug: Apatinib Mesylate; Drug: ifosfamide and etoposide

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• histological diagnosis of osteosarcoma (confirmed by central pathological review by an expert pathologist from the Peking University People's Hospital)
• objective disease progression within 3 months prior to treatment according to RECIST 1.1
• previously treated with one to two lines of chemotherapy for metastatic disease
• have an adequate performance status (adults:Eastern Cooperative Oncology Group [ECOG] performance status of 0-1;children aged >12 years: a score of ≥60% on the Karnofsky performance scale; children aged ≤12 years a score of ≥60% on the Lansky scale)

Exclusion Criteria:

• a life expectancy of less than 3 months
• patients had to have adequate bone marrow function, normal renal function, normal liver function, and normal pancreatic function
• no other malignant tumors
• no malignant pleural and peritoneal effusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Apatinib+IE	Drug: Apatinib Mesylate; apatinib orally daily and ifosfamide 1.8mg/m2/d d1-3, etoposide 100mg/m2/d d1-3; Other Names: ifosfamide and etoposide; Drug: ifosfamide and etoposide; ifosfamide and etoposide
ACTIVE_COMPARATOR: IE	Drug: ifosfamide and etoposide; ifosfamide and etoposide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
event-free survival	from start treatment to any events/death	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival	from start treatment to progression/death	24 months
overall survival	from start treatment to death	24 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Xie L, Xu J, Sun X, Tang X, Yan T, Yang R, Guo W. Apatinib for Advanced Osteosarcoma after Failure of Standard Multimodal Therapy: An Open Label Phase II Clinical Trial. Oncologist. 2019 Jul;24(7):e542-e550. doi: 10.1634/theoncologist.2018-0542. Epub 2018 Dec 17.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2020
• Primary Completion (ACTUAL): March 1, 2021
• Study Completion (ACTUAL): June 1, 2021

Study Registration Dates

• First Submitted: December 26, 2020
• First Submitted That Met QC Criteria: December 26, 2020
• First Posted (ACTUAL): December 30, 2020

Study Record Updates

• Last Update Posted (ACTUAL): March 15, 2022
• Last Update Submitted That Met QC Criteria: March 12, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: prognosis; apatinib; osteosarcoma; toxicity; ifosfamide and etoposide
• 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; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Protein Kinase Inhibitors; Etoposide; Etoposide phosphate; Ifosfamide; Isophosphamide mustard; Apatinib
• Other Study ID Numbers: PKUPH-sarcoma 14

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