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

Byung-Kiu Park

Status and phase: Unknown; Phase 2

Conditions: Osteosarcoma; Feasibility; Biomarker; Treatment Response

Treatments: Drug: Good responder group adjuvant chemotherapy; Drug: Poor responder group adjuvant chemotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT03390946

NCC-OSA-1601

Details and patient eligibility

About

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.

Full 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.

Enrollment: 23 estimated patients

Sex: All

Ages: Under 40 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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23 participants in 1 patient group

four-drug interval-compressed regimen

Experimental group

Description:

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'.

Treatment:

Drug: Poor responder group adjuvant chemotherapy

Drug: Good responder group adjuvant chemotherapy