Clinical trial NCT05277480: Apatinib With Ifosfamide Plus Etoposide for Relapsed or Refractory Osteosarcoma (OAIE)
Official title: Apatinib in Combination With Ifosfamide and Etoposide (IE) for Relapsed or Refractory Osteosarcoma Progressed Upon First-line Chemotherapy (AIEO): a Prospective, Multiple-centre, Two-arm, Phase 2 Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Effect of Drug
Drug
Toxicity
Keywords: Osteosarcoma
Apatinib
Ifosfamide
Etoposide
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
Collaborators: name: Jiangsu HengRui Medicine Co., Ltd.
First posted: 2022-03-14
Enrollment: 81
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. advanced recurrent and refractory osteosarcoma confirmed by histopathology;
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 ≤ 1 ;
6. acceptable haematologic, hepatic, and renal function.

Exclusion Criteria:

1. those who had been previously treated with antiangiogenic TKIs and single IE chemotherapy;
2. 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.;
3. 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;
4. weight loss of 20% or more before illness;
5. brain or leptomeningeal metastasis;
6. surgical procedure or radiotherapy within 4 weeks of enrollment;
7. activegastroduodenal ulcer, previous condition associated with risk of bleeding or requiring anticoagulation;
8. proteinuria or hematuria, denutrition with albuminemia \<25 g/L;
9. women who were pregnant or breast feeding, other malignancy;
10. positive HBV/HCV/HIV serology, and known allergy to the experimental agents.

Primary outcomes:
measure: Progression free survival
timeFrame: 2 years
Secondary outcomes:
measure: Overall survival
timeFrame: 3 years
Other outcomes:
measure: Objective response rate
timeFrame: 2 years
measure: Disease control rate
timeFrame: 2 years
measure: Duration of response
timeFrame: 2 years
measure: Time to response
timeFrame: 2 years
measure: Time to progress
timeFrame: 2 years
measure: Progression-free survival at 4 months
timeFrame: 2 years
measure: Progression-free survival at 6 months
timeFrame: 2 years
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Nanjing
country: China
facility: Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University
state: Jiangsu
city: Shanghai
country: China
facility: Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Jiao Tong University Affiliated Sixth People's Hospital
state: Shanghai
Study officials:
References: