Clinical trial NCT03742193: Pulmonary Resectable Metastases of Osteosarcoma With Anti-angiogenics and CHemotherapy
Official title: A Phase II Study of Gemcitabine-docetaxel Chemotherapy With Anti-angiogenic Therapy for Pulmonary Resectable Metastases of Osteosarcoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Osteosarcoma
Pulmonary Metastases
Apatinib
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2018-11-15
Enrollment: 43
Sex: ALL
Minimum age (years): 10
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 12 months Progression-free survival rate(12mPFR)
timeFrame: 12 months from the recruitment of the study
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Baseline until death, followed through study completion, an average of 2 years
measure: Total resectability
timeFrame: after neoadjuvant systemic therapy, an average of 8~9 weeks
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: through study completion, an average of 1 years
measure: Objective response rate (ORR)
timeFrame: after neoadjuvant systemic therapy, an average of 8~9 weeks
measure: Clinical benefit rate (CBR)
timeFrame: after neoadjuvant systemic therapy, an average of 8~9 weeks
measure: Progression free survival (PFS)
timeFrame: Baseline until disease progression or death, whichever occurs first (followed through study completion, an average of 1.5 years)
measure: OS rate
timeFrame: 12 and 24 months from baseline
Other outcomes:
measure: Exploratory outcome: Subgroup analysis of progression-free survival(PFS)
timeFrame: Baseline until disease progression or death, whichever occurs first (followed through study completion, an average of 1.5 years)
measure: Exploratory outcome: The correlation of potential pathological biomarker with PFS
timeFrame: Baseline until disease progression or death, whichever occurs first (followed through study completion, an average of 1.5 years)
measure: Exploratory outcome: Tumor response pre-metastasectomy as a predictor of PFS
timeFrame: Baseline until disease progression or death, whichever occurs first (followed through study completion, an average of 1.5 years)
measure: Exploratory outcome: Tumor cavitation as a prognostic factor for oncological outcome
timeFrame: Baseline until disease progression or death, whichever occurs first (followed through study completion, an average of 1.5 years)
measure: Exploratory outcome: AEs of the targeted therapy as prognostic factors for oncological outcome, especially pulmonary lesion cavitation/pneumothorax and hair depigmentation
timeFrame: Baseline until disease progression or death, whichever occurs first (followed through study completion, an average of 1.5 years)
measure: Correlation of KDR 604 polymorphism with pulmonary lesion cavitation/pneumothorax and with PFS
timeFrame: Baseline until disease progression or death, whichever occurs first (followed through study completion, an average of 1.5 years)
measure: Exploratory outcome: 1.0-mm CT scan for the early identification small lung nodule as pulmonary recurrence
timeFrame: Baseline until disease progression or death, whichever occurs first (followed through study completion, an average of 1.5 years)
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: Ruijin Hospital
name: Weibin Zhang, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: