Neoplasms

All Conditions

Symptoms and General Pathology

Rare Diseases

Sarcoma

Disease Progression

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Anti-Bacterial Agents

Doxorubicin

Liposomal doxorubicin

Ifosfamide

Antibiotics, Antitubercular

Dacarbazine

Isophosphamide mustard

Pirarubicin

Enzyme Inhibitors

participants will recieve pegylated liposomal doxorubicin (50 mg/m²d1) plus ifosfamide (2 g/m²/d d2-3), dacarbazine (300 mg/m²/d d2-3).

participants will recieve pirarubicin (60 mg/m²d1) plus ifosfamide (2 g/m²/d d2-3), dacarbazine (300 mg/m²/d d2-3).

Several efforts have been made to improve the toxicity profile of conventional anthracyclines, including the use of liposomal encapsulation technology,such as pegylated liposomal doxorubicin.

pegylated liposomal doxorubicin

Another effort has been made to improve the toxicity profile of conventional anthracyclines is the development of novel anthracycline analogs,such as pirarubicin.

pirarubicin

Wei Guo, M.D.and Ph.D.

Advanced soft tissue sarcoma patients who have previously recieved anthracyclines might still benefit from doxorubicin, ifosfamide and dacarbazine. However doxorubicin might be stopped using because of chronic cumulative heart toxicity. Several efforts have been made to improve the toxicity profile of conventional anthracyclines, including the use of liposomal encapsulation technology and the development of novel anthracycline analogs,such as pegylated liposomal doxorubicin and pirarubicin. However their actual effectiveness and toxicity have not been studied in prospective trial. The purpose of the study is to investigate whether they are available for this group of patients.

We design this multicentre, open-label, randomised, phase 2 trial at 5 academic hospitals in China. Eligible patients need to be aged 16 years or older with a diagnosis of an advanced unresectable or metastatic soft-tissue sarcoma, of intermediate or high grade, for which no standard curative therapy will be available, an Eastern Cooperative Oncology Group performance status of 0-1, and measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1.

Participants will be randomly assigned (1:1) to receive pegylated liposomal doxorubicin (60 mg/m² via continuous intravenous infusion for 4-6 h on day 1 of every 21-day cycle for up to six cycles) or pirarubicin (30 mg/m2/d continuous intravenous infusion for 3h on day 1 and 2 of every 21-day cycle for up to six cycles) plus ifosfamide ( 2 g/m²/d intravenously for 2h on day 2,3 and 4 of every 21-day cycle for up to six cycles), dacarbazine (300 mg/m²/d intravenously for 2h on day 2,3 and 4 of every 21-day cycle for up to six cycles ).After six cycles of treatment, patients will be followed up expectantly whereas patients with stable or responsive disease are allowed to continue with ifosfamide and dacarbzine until documented disease progression. A web-based central randomisation with block sizes of two and four was stratified by extent of disease, drug administration method, and previous systemic therapy. Patients and investigators will not be masked to treatment assignment. The primary endpoint is progression survival, analysed in the intention-to-treat population. Safety analyses will be done in all patients who receive any amount of study drug.

Patients will be randomly assigned (1:1) to receive pegylated liposomal doxorubicin (50 mg/m² on day 1 of every 21-day cycle for up to six cycles) or pirarubicin (60 mg/m² on day 1 of every 21-day cycle for up to six cycles) plus ifosfamide (2 g/m²/d d2-4 of every 21-day cycle for up to six cycles) and dacarbazine (300 mg/m²/d d2-4 of every 21-day cycle for up to six cycles).

A web-based central randomisation with block sizes of two and four was stratified by extent of disease,anthracycline administration method, and previous systemic therapy. Participants and investigators will not be masked to treatment assignment. The primary endpoint will be assessed in the intention-to-treat population. The outcome assessors will be masked to the two research groups.

Pegylated Liposomal Doxorubicin Versus Pirarubicin Plus Ifosfamide, Dacarbazine in Locally Advanced, Unresectable or Metastatic Soft-tissue Sarcoma

Comparing the Effectiveness and Toxicity for Locally Advanced, Unresectable or Metastatic Soft-tissue Sarcoma Patients Who Had Received Total Dose of Anthracycline Antibiotics More Than 300mg/m2 With Pegylated Liposomal Doxorubicin Versus Pirarubicin Plus Ifosfamide, Dacarbazine, a Multicentre, Open-label, Randomised Phase 2 Trial

Progression-free survival is defined as time from randomisation to the first occurrence of progression of disease or death from any cause within 63 days of last response assessment or randomisation.

overall survival is defined as the duration from date of randomisation to the date of death from any cause.

objective response rate includes complete and partial responses as defined by RECIST version 1.1.

We use ultrasound to routinely estimate the left ventricular ejection fraction function.

Spots Global Cancer Trial Database for toxicity for heart