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

May 15, 2020 updated by: Peking University People's Hospital

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

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.

Study Overview

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 Type

Interventional

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Beijing, China, 100044
        • Peking University People's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A
participants will recieve pegylated liposomal doxorubicin (50 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.
Placebo Comparator: Arm B
participants will recieve pirarubicin (60 mg/m²d1) plus ifosfamide (2 g/m²/d d2-3), dacarbazine (300 mg/m²/d d2-3).
Another effort has been made to improve the toxicity profile of conventional anthracyclines is the development of novel anthracycline analogs,such as pirarubicin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
progression-free survival
Time Frame: 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.
12 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 6, 2017

Primary Completion (Anticipated)

November 15, 2020

Study Completion (Anticipated)

December 30, 2020

Study Registration Dates

First Submitted

November 8, 2017

First Submitted That Met QC Criteria

November 9, 2017

First Posted (Actual)

November 14, 2017

Study Record Updates

Last Update Posted (Actual)

May 19, 2020

Last Update Submitted That Met QC Criteria

May 15, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Sharing Supporting Information Type

  • Statistical Analysis Plan (SAP)
  • Clinical Study Report (CSR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Toxicity

Clinical Trials on pegylated liposomal doxorubicin

3
Subscribe