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

Phase 2

Withdrawn

• Conditions: Progression-free Survival; Overall Survival; Toxicity
• Interventions: Drug: pirarubicin; Drug: pegylated liposomal doxorubicin

• Registration Number: NCT03342300
• Lead Sponsor: Peking University People's Hospital

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2017-11-06
• Study First Submitted: 2017-11-08
• Study First Submitted QC: 2017-11-09
• Study First Posted: 2017-11-14
• Status Verified: 2020-05
• Last Update Submitted: 2020-05-15
• Last Update Posted: 2020-05-19
• Primary Completion: 2020-11-15
• Study Completion: 2020-12-30

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• 16 years or older;
• diagnosis of an advanced unresectable or metastatic soft tissue sarcoma, of intermediate or high grade, for which no standard curative therapy is available;
• cumulative dose of anthracycline antibiotic ≥ 300mg/m2;
• stable or responsive to doxorubicin, potential beneficiary;
• an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, a life expectancy of at least 3 months;
• measurable disease according to RECIST 1.1;
• adequate end-organ and haemopoietic function.

Exclusion Criteria

• progress over doxorubicin;
• previous mediastinal or cardiac radiotherapy;
• a low-grade tumour according to standard grading systems (eg, American Joint Committee on Cancer grade 1 and 2 or Fédération Nationale des Centres de Lutte Contre le Cancer grade 1);
• significant cardiac dysfunction;
• severe chronic obstructive pulmonary disease;
• a known infection with HIV or active infection with hepatitis B or hepatitis C;
• known brain metastases unless previously treated and well controlled for a period of 3 months or longer;
• combination with other anti-tumor therapy;
• pregnant or breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B	pirarubicin	participants will recieve pirarubicin (60 mg/m²d1) plus ifosfamide (2 g/m²/d d2-3), dacarbazine (300 mg/m²/d d2-3).
Arm A	pegylated liposomal doxorubicin	participants will recieve pegylated liposomal doxorubicin (50 mg/m²d1) plus ifosfamide (2 g/m²/d d2-3), dacarbazine (300 mg/m²/d d2-3).

Primary Outcome Measures

Name	Time	Method
progression-free survival	12 weeks	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.

Secondary Outcome Measures

Name	Time	Method
overall survival	12 months	overall survival is defined as the duration from date of randomisation to the date of death from any cause.
objective response rate, ORR	12 weeks	objective response rate includes complete and partial responses as defined by RECIST version 1.1.
left ventricular ejection fraction function	12 months	We use ultrasound to routinely estimate the left ventricular ejection fraction function.

Trial Locations

Locations (1)

Peking University People's Hospital; 🇨🇳 Beijing, China