Biomarker, Feasibility, Osteosarcoma, Treatment Response
Conditions
Keywords
four-drugs, interval-compression
Brief summary
The aim of the study is to test the feasibility of four-drug, interval-compressed regimen in osteosarcoma. Primary objective is to explore the toxicity and mortality related to treatment. Secondary objectives are to examine tumor necrosis rates after neoadjuvant chemotherapy, and to evaluate the usefulness of circulating cell-free DNA, survivin, or transforming growth factor-beta1 levels as well as programmed cell death ligand 1 expression in tumor specimen as a predictive or prognostic biomarker in osteosarcoma patients.
Detailed description
In this study, the investigators will investigate the feasibility of interval compressed regimen using four-drugs in newly-diagnosed osteosarcoma patients. Four drugs will be adriamycin, high-dose methotrexate, cisplatin, ifosfamide. All these drugs will be given preoperatively in an interval-compressed schedule, but postoperatively at a regular interval. Neoadjuvant therapy will be composed of two courses, and adjuvant therapy of two or three courses depending on necrosis rates following neoadjuvant therapy.
Interventions
DRUGPoor responder group adjuvant chemotherapy
Poor responder group (necrosis ≤ 90%) : week 0, 7 and 14, doxorubicin; week 2, 9 and 16, ifosfamde, week 4, 11, 18 and 19, methotrexate; wk 5, 12 and 20 B. Resection of tumor C. Adjuvant chemotherapy 1. Poor responder group (necrosis ≤ 90%) * week 0, 7 and 14, doxorubicin; week 2, 9 and 16, ifosfamde, week 4, 11, 18 and 19, methotrexate; wk 5, 12 and 20 2. Good responder group (necrosis \> 90%) * week 0 and 8, doxorubicin; week 2 and 10, ifosfamide; week 4, 5, 12 and 13, methotrexate; week 6 and 14, cisplatin
DRUGGood responder group adjuvant chemotherapy
Good responder group (necrosis \> 90%) : week 0 and 8, doxorubicin; week 2 and 10, ifosfamide; week 4, 5, 12 and 13, methotrexate; week 6 and 14, cisplatin
Sponsors
Samsung Medical Center
Chungnam National University Hospital
Byung-Kiu Park
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 40 Years
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed osteosarcoma patients under age 40 years.
Exclusion criteria
* Patients who don't meet the organ function criteria as follows; 1. renal function : CCr or GFR or eGFR ≥ 70 mL/min/1.73 m2 2. liver function : AST/ALT ≤ 5 x upper limit, total bilirubin ≤ 1.5 x upper limit of normal for age 3. cardiac function : shortening fraction ≥ 24% or ejection fraction ≥ 50% (Echo) 4. lung function : No dyspnea on rest, If dyspnea exists, SpO2 95% or more in room air by pulse oximetry, 5. hematologic : ANC ≥ 750/uL and platelet ≥ 75,000/uL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity determined according to CTCAE | Until study completion, an average of 3 years | treatment-related toxicity (organ dysfunction, neutropenic fever, infection, mortality, et al.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| tumor necrosis rate | Until study completion, an average of 3years | necrosis rate of the excised tumor after neoadjuvant chemotherapy |
| Predictive or prognostic biomarker | Until study completion, an average of 3 years | Usefulness of circulating cell-free DNA, survivin, transforming growth factor-beta1 levels and programmed cell death 1 expression in tumor specimen as a biomarker |
Countries
South Korea
Contacts
Primary ContactByung-Kiu Park, M.D., Ph.D.
Outcome results
None listed