Feasibility Study of Interval Compressed Regimen Using Four-drugs for Osteosarcoma

Phase 2

• Conditions: Osteosarcoma; Feasibility; Treatment Response; Biomarker
• Interventions: Drug: Poor responder group adjuvant chemotherapy; Drug: Good responder group adjuvant chemotherapy

• Registration Number: NCT03390946
• Lead Sponsor: Byung-Kiu Park

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.

Study Timeline

• Study First Submitted: 2017-12-11
• Study First Submitted QC: 2017-12-28
• Status Verified: 2018-01
• Study First Posted: 2018-01-05
• Last Update Submitted: 2018-01-05
• Last Update Posted: 2018-01-09
• Study Start: 2018-02-01
• Primary Completion: 2020-12-31
• Study Completion: 2020-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 23

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
four-drug interval-compressed regimen	Poor responder group adjuvant chemotherapy	Interventions for 'four-drug interval-compressed regimen': Drug: methotrexate, cisplatin, doxorubicin, ifosfamide. Newly diagnosed oseteosarcoma patients under 40 years are eligible. Neoadjuvant chemotherapy with four drugs in an interval-compressed schedule will be done as a single arm. Duration of neoadjuvant chemotherapy will be 10 weeks like that of conventional three-drug regimen, although four-drugs are employed in the current protocol. After tumor resection operation, participants will be divided to poor responder group and good responder group based on 90% necrosis rate of a tumor specimen. Poor responder group and will be assigned to 'Poor responder group adjuvant chemotherapy' and good responder will be assigned to 'Good responder group adjuvant chemotherapy'.
four-drug interval-compressed regimen	Good responder group adjuvant chemotherapy	Interventions for 'four-drug interval-compressed regimen': Drug: methotrexate, cisplatin, doxorubicin, ifosfamide. Newly diagnosed oseteosarcoma patients under 40 years are eligible. Neoadjuvant chemotherapy with four drugs in an interval-compressed schedule will be done as a single arm. Duration of neoadjuvant chemotherapy will be 10 weeks like that of conventional three-drug regimen, although four-drugs are employed in the current protocol. After tumor resection operation, participants will be divided to poor responder group and good responder group based on 90% necrosis rate of a tumor specimen. Poor responder group and will be assigned to 'Poor responder group adjuvant chemotherapy' and good responder will be assigned to 'Good responder group adjuvant chemotherapy'.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

National Cancer Center; 🇰🇷 Goyang-si, Gyeonggi, Korea, Republic of