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

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



Sponsors


Source

Peking University People's Hospital

Oversight Info

Has Dmc

Yes

Is Fda Regulated Drug

No

Is Fda Regulated Device

No


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.

Overall Status

Recruiting

Start Date

2017-11-06

Completion Date

2019-12-30

Primary Completion Date

2019-11-15

Phase

Phase 2/Phase 3

Study Type

Interventional

Primary Outcome

Measure

Time Frame

progression-free survival
12 weeks

Secondary Outcome

Measure

Time Frame

overall survival
12 months
objective response rate, ORR
12 weeks
toxicity for heart
12 months

Enrollment

100

Conditions


Intervention

Intervention Type

Drug

Intervention Name


Description

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.

Arm Group Label

Arm A


Intervention Type

Drug

Intervention Name


Description

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

Arm Group Label

Arm B



Eligibility

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.

Gender

All

Minimum Age

16 Years

Maximum Age

N/A

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Wei Guo, M.D.and Ph.D.
Principal Investigator
Musculoskeletal Tumor Center of Peking University People's Hospital

Overall Contact

Last Name

Lu Xie, M.D.

Phone

+86-13401044719

Email



Location

Facility

Status

Contact

Investigator

Peking University People's Hospital
Beijing 100044 China
Recruiting
Last Name: Tingting Ren, Ph.D.
Phone: +86-13810095026
Email: [email protected]
Last Name: Wei Guo, M.D. and Ph.D.
Role: Principal Investigator

Location Countries

Country

China


Verification Date

2017-11-01

Lastchanged Date

2017-11-09

Firstreceived Date

2017-11-08

Responsible Party

Responsible Party Type

Sponsor


Keywords


Has Expanded Access

No

Condition Browse


Number Of Arms

2

Intervention Browse

Mesh Term

Doxorubicin

Liposomal doxorubicin

Isophosphamide mustard

Pirarubicin

Ifosfamide



Arm Group

Arm Group Label

Arm A

Arm Group Type

Experimental

Description

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


Arm Group Label

Arm B

Arm Group Type

Placebo Comparator

Description

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



Firstreceived Results Date

N/A

Overall Contact Backup

Last Name

Jie Xu, M.D.

Phone

+86-15901040835

Email



Reference

Citation

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Acronym

PDVPSTS

Firstreceived Results Disposition Date

N/A

Study Design Info

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).

Primary Purpose

Treatment

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.


Study First Submitted

November 8, 2017

Study First Submitted Qc

November 9, 2017

Study First Posted

November 14, 2017

Last Update Submitted

November 9, 2017

Last Update Submitted Qc

November 9, 2017

Last Update Posted

November 14, 2017


ClinicalTrials.gov processed this data on November 14, 2017

Conditions

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Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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