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

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ClinicalTrials.gov Identifier: NCT03342300
Recruitment Status : Recruiting
First Posted : November 14, 2017
Last Update Posted : November 17, 2017
Sponsor:
Collaborators:
Peking University Shougang Hospital
Chinese PLA General Hospital
Beijing Jishuitan Hospital
Xijing Hospital
gwcmc
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Progression-free Survival Overall Survival Toxicity Drug: pegylated liposomal doxorubicin Drug: pirarubicin Phase 2 Phase 3

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  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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).
Masking: Single (Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 6, 2017
Estimated Primary Completion Date : November 15, 2019
Estimated Study Completion Date : December 30, 2019


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).
Drug: pegylated liposomal doxorubicin
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).
Drug: pirarubicin
Another effort has been made to improve the toxicity profile of conventional anthracyclines is the development of novel anthracycline analogs,such as pirarubicin.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. objective response rate, ORR [ Time Frame: 12 weeks ]
    objective response rate includes complete and partial responses as defined by RECIST version 1.1.

  3. left ventricular ejection fraction function [ Time Frame: 12 months ]
    We use ultrasound to routinely estimate the left ventricular ejection fraction function.



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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03342300


Contacts
Contact: Lu Xie, M.D. +86-13401044719 sweetdoctor@163.com
Contact: Jie Xu, M.D. +86-15901040835 xujie_pkuph@sina.com

Locations
China
Peking University People's Hospital Recruiting
Beijing, China, 100044
Contact: Tingting Ren, Ph.D.    +86-13810095026    tumorcenter@163.com   
Principal Investigator: Wei Guo, M.D. and Ph.D.         
Sponsors and Collaborators
Peking University People's Hospital
Peking University Shougang Hospital
Chinese PLA General Hospital
Beijing Jishuitan Hospital
Xijing Hospital
gwcmc
Investigators
Principal Investigator: Wei Guo, M.D.and Ph.D. Musculoskeletal Tumor Center of Peking University People's Hospital

Publications:

Responsible Party: Peking University People's Hospital
ClinicalTrials.gov Identifier: NCT03342300     History of Changes
Other Study ID Numbers: CBTRA-03
First Posted: November 14, 2017    Key Record Dates
Last Update Posted: November 17, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
URL: http://

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Peking University People's Hospital:
soft tissue sarcoma
pegylated liposomal doxorubicin
pirarubicin
toxicity for heart
cumulative dose

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Doxorubicin
Liposomal doxorubicin
Isophosphamide mustard
Pirarubicin
Ifosfamide
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents