Pulmonary Resectable Metastases of Osteosarcoma With Anti-angiogenics and CHemotherapy (PROACH)

Shanghai Jiao Tong University

Status and phase: Active, not recruiting; Phase 2

Conditions: Osteosarcoma; Apatinib; Pulmonary Metastases

Treatments: Drug: GD regimen; Drug: Apatinib

Study type: Interventional

Funder types: Other

Identifiers

NCT03742193

2018LLS-NO.84-3

Details and patient eligibility

About

The aim of this study is to evaluate the efficacy and safety of Second-line chemotherapy combined with Apatinib for the patients with resectable pulmonary metastasis of osteosarcoma.

Full description

After standard chemotherapy and surgery for the localized disease, pulmonary metastases of osteosarcoma occurs in up to 40% of cases and still remain challenging without satisfactory regimen. Apatinib is a oral kinase inhibitor of receptor tyrosine targeting VEGFR2. A pilot study indicated that Apatinib improved the PFS after multi-line chemotherapy failure, and might partly reversed chemo-refractory status for advanced osteosarcoma. Thus, the investigators explored the efficacy of combining Apatinib with current available second-line chemotherapy compared to chemotherapy alone for treating first resectable pulmonary metastases of osteosarcoma following the failure of first-line chemotherapy and wide/radical-margin surgery. Participants will receive 250 mg of apatinib twice daily combined with gemcitabine-docetaxel (GD) regimen before and after the surgical resection of the pulmonary metastases. Osteosarcoma patients with pulmonary recurrence only at baseline will be recruited in the study. The primary end point is progression-free survival rate (PFR) compared with historical control. A12 month PFR of 30% or less is considered inactive, while a 12 month PFR of 50% or greater is regarded as of interest for additional development. With a type I error rate of 5% and a power of 83%, the number of patients needed for this design is 43.

Enrollment: 43 estimated patients

Sex: All

Ages: 10 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• age between 10 and 50 years;
• diagnosis of histologically confirmed high grade osteosarcoma;
• identification of pulmonary metastases without the existence of local recurrence(previous re-resection of local recurrence with wide margin is allowed).
• resectable pulmonary nodule(s), defined as nodule(s) that are removable by wedge resection/ segmentectomy/lobectomy without necessitating a pneumonectomy (e.g., nodules immediately adjacent to the main stem bronchus or main pulmonary vessels)
• prior treatment consisted of standard National Comprehensive Cancer Network (NCCN) guideline recommended first-line chemotherapy
• wide/radical-margin surgical resection of the primary tumor completed at least 4 weeks before enrollment.
• Eastern Cooperative Oncology Group(ECOG) performance status 0-2 with a life expectancy >3 months;
• adequate renal, hepatic, and hemopoietic function;
• normal or controlled blood pressure;
• no thoracic comorbidities with adequate pulmonary function eligible for thoracic surgery

Exclusion criteria

• previously exposed to GD chemotherapy or VEGFR2 Tyrosine-kinase inhibitors (TKIs);
• existence of local recurrence;
• 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 or Hemorrhagic diseases ;
• metastases considered unresectable or borderline resectable at baseline
• intolerable of thoracis surgery
• pleural or peritoneal effusion that needs to be handled by surgical treatment;
• combined with other infections or wounds
• wound dystrophy, poor soft-tissue around implantation or other wound complications risky of non-healing given angiogenesis inhibitor assessed by the investigators

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

43 participants in 1 patient group

Apatinib + GD group

Experimental group

Description:

Apatinib + GD regimen. For unilateral metastases,3 cycles before metastasectomy, and 4 cycles after. For bilateral metastases, 3 cycles before first metastasectomy, 1 cycle inbetween, and then second metastasectomy followed by 4 cycles. Apatinib monotherapy is then maintained until 1 year following complete resection.

Treatment:

Drug: GD regimen

Drug: Apatinib