Pulmonary Resectable Metastases of Osteosarcoma With Anti-angiogenics and CHemotherapy

NCT03742193 | Unknown Phase 2 DMC

• 1 other identifier: 2018LLS-NO.84-3
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteosarcoma; Pulmonary Metastases; Apatinib

Outcome Measures

Primary Outcomes (1)

• 12 months Progression-free survival rate(12mPFR)

  The proportion of patients with progression-free survival at 12 months according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). A 12mPFR of 30% or less is considered inactive, while a 12mPFR of 50% or greater is regarded as of interest for additional development

  12 months from the recruitment of the study

Secondary Outcomes (7)

• Overall survival (OS)

  Baseline until death, followed through study completion, an average of 2 years

• Total resectability

  after neoadjuvant systemic therapy, an average of 8~9 weeks

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  through study completion, an average of 1 years

• Objective response rate (ORR)

  after neoadjuvant systemic therapy, an average of 8~9 weeks

• Clinical benefit rate (CBR)

  after neoadjuvant systemic therapy, an average of 8~9 weeks

Other Outcomes (7)

• Exploratory outcome: Subgroup analysis of progression-free survival(PFS)

  Baseline until disease progression or death, whichever occurs first (followed through study completion, an average of 1.5 years)

• Exploratory outcome: The correlation of potential pathological biomarker with PFS

  Baseline until disease progression or death, whichever occurs first (followed through study completion, an average of 1.5 years)

• Exploratory outcome: Tumor response pre-metastasectomy as a predictor of PFS

  Baseline until disease progression or death, whichever occurs first (followed through study completion, an average of 1.5 years)

Study Arms (1)

Apatinib + GD group

EXPERIMENTAL

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.

Drug: Apatinib; Drug: GD regimen

Interventions

Apatinib DRUG

Apatinib 250mg tablet by mouth, bid. 48 hrs break before and 96 hrs after the surgical resection of the pulmonary metastases.

Also known as: VEGFR Inhibitor

Apatinib + GD group

GD regimen DRUG

One cycle: gemcitabine 900 mg/m\^2 over 90 min on Day 1, and gemcitabine 900 mg/m\^2 and docetaxel 75 mg/m\^2 on Day 8. Every 21 days were eligible. 1\~2 -week break before and 2-week break after the surgical resection of the pulmonary metastases is taken.

Also known as: Chemotherapy

Apatinib + GD group

Eligibility Criteria

• Age: 10 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

MeSH Terms

Conditions

Osteosarcoma

Interventions

apatinib; Drug Therapy

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Weibin Zhang, PhD, MD

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: An Independent radiologic reviewing committee assess the radiological tumor response in a blinded manner. Data Safety and Monitoring Board (DSMB) access the outcome in the interim analysis and final analysis
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 25, 2018
• First Posted: November 15, 2018
• Study Start: August 11, 2019
• Primary Completion: November 15, 2023
• Study Completion: December 30, 2023
• Last Updated: November 1, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)