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Progression-free SurvivalPhase 2/3PDVPSTSNCT03342300

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

A Phase 2/3 study testing pegylated liposomal doxorubicin and pirarubicin in people with Progression-free Survival and Overall Survival, run by Peking University People's Hospital at 1 site in China.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 16 years and older
What is being tested?
pegylated liposomal doxorubicin and pirarubicin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
1 siteChina
Study dates
6 Nov 2017to 30 Dec 2020
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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;
Show all 9Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Peking University People's Hospital

    Beijing, 100044

Other trials in China

About this study

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

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.

Read the 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.

Being tested
pegylated liposomal doxorubicin, pirarubicin
Keywords
soft tissue sarcoma, pegylated liposomal doxorubicin, pirarubicin, toxicity for heart, cumulative dose
Medical subject headings
Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • pegylated liposomal doxorubicinDrug

    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.

  • pirarubicinDrug

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

Study groups in NCT03342300
Study groupRoleWhat they receive
Arm AExperimentalparticipants will recieve pegylated liposomal doxorubicin (50 mg/m²d1) plus ifosfamide (2 g/m²/d d2-3), dacarbazine (300 mg/m²/d d2-3).
Receives: Drug: pegylated liposomal doxorubicin
Arm BPlacebo comparatorparticipants will recieve pirarubicin (60 mg/m²d1) plus ifosfamide (2 g/m²/d d2-3), dacarbazine (300 mg/m²/d d2-3).
Receives: Drug: pirarubicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. progression-free survival

    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.

    Measured: 12 weeks

Secondary outcomes (3)

  1. overall survival

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

    Measured: 12 months

  2. objective response rate, ORR

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

    Measured: 12 weeks

  3. left ventricular ejection fraction function

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

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Nov 2017
  2. Study start6 Nov 2017
  3. Primary completion15 Nov 2020 (estimated)
  4. Study completion30 Dec 2020 (estimated)

Why it stopped: No participants enrolled

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
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 blind
Who is masked
Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03342300
Sponsor's protocol ID
CBTRA-03
Acronym
PDVPSTS
Status last verified
May 2020
First submitted
8 Nov 2017
Last updated
19 May 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Frezza AM, Stacchiotti S, Gronchi A. Systemic treatment in advanced soft tissue sarcoma: what is standard, what is new. BMC Med. 2017 Jun 2;15(1):109. doi: 10.1186/s12916-017-0872-y.

    PubMed 28571564

  • Antman K, Crowley J, Balcerzak SP, Rivkin SE, Weiss GR, Elias A, Natale RB, Cooper RM, Barlogie B, Trump DL, et al. An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol. 1993 Jul;11(7):1276-85. doi: 10.1200/JCO.1993.11.7.1276.

    PubMed 8315425

  • Jelic S, Kovcin V, Milanovic N, Babovic N, Kreacic M, Ristovic Z, Vlajic M, Filipovic-Ljeskovic I. Randomised study of high-dose epirubicin versus high-dose epirubicin-cisplatin chemotherapy for advanced soft tissue sarcoma. Eur J Cancer. 1997 Feb;33(2):220-5. doi: 10.1016/s0959-8049(96)00297-3.

    PubMed 9135492

  • Le Cesne A, Judson I, Crowther D, Rodenhuis S, Keizer HJ, Van Hoesel Q, Blay JY, Frisch J, Van Glabbeke M, Hermans C, Van Oosterom A, Tursz T, Verweij J. Randomized phase III study comparing conventional-dose doxorubicin plus ifosfamide versus high-dose doxorubicin plus ifosfamide plus recombinant human granulocyte-macrophage colony-stimulating factor in advanced soft tissue sarcomas: A trial of the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 2000 Jul;18(14):2676-84. doi: 10.1200/JCO.2000.18.14.2676.

    PubMed 10894866

  • Santoro A, Tursz T, Mouridsen H, Verweij J, Steward W, Somers R, Buesa J, Casali P, Spooner D, Rankin E, et al. Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 1995 Jul;13(7):1537-45. doi: 10.1200/JCO.1995.13.7.1537.

    PubMed 7602342

  • Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R Jr, Conti I, Cosaert J, Schwartz GK. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97. doi: 10.1016/S0140-6736(16)30587-6. Epub 2016 Jun 9.

    PubMed 27291997

  • Bui-Nguyen B, Butrynski JE, Penel N, Blay JY, Isambert N, Milhem M, Kerst JM, Reyners AK, Litiere S, Marreaud S, Collin F, van der Graaf WT; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC/STBSG) and the Sarcoma Alliance for Research through Collaboration (SARC). A phase IIb multicentre study comparing the efficacy of trabectedin to doxorubicin in patients with advanced or metastatic untreated soft tissue sarcoma: the TRUSTS trial. Eur J Cancer. 2015 Jul;51(10):1312-20. doi: 10.1016/j.ejca.2015.03.023. Epub 2015 Apr 23.

    PubMed 25912752

  • Schoffski P, Ray-Coquard IL, Cioffi A, Bui NB, Bauer S, Hartmann JT, Krarup-Hansen A, Grunwald V, Sciot R, Dumez H, Blay JY, Le Cesne A, Wanders J, Hayward C, Marreaud S, Ouali M, Hohenberger P; European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG). Activity of eribulin mesylate in patients with soft-tissue sarcoma: a phase 2 study in four independent histological subtypes. Lancet Oncol. 2011 Oct;12(11):1045-52. doi: 10.1016/S1470-2045(11)70230-3. Epub 2011 Sep 19.

    PubMed 21937277

  • Lefrak EA, Pitha J, Rosenheim S, Gottlieb JA. A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer. 1973 Aug;32(2):302-14. doi: 10.1002/1097-0142(197308)32:23.0.co;2-2. No abstract available.

    PubMed 4353012

  • Vondrakova D, Malek F, Ostadal P, Vranova J, Miroslav P, Schejbalova M, Neuzil P. Correlation of NT-proBNP, proANP and novel biomarkers: copeptin and proadrenomedullin with LVEF and NYHA in patients with ischemic CHF, non-ischemic CHF and arterial hypertension. Int J Cardiol. 2011 Aug 4;150(3):343-4. doi: 10.1016/j.ijcard.2011.05.029. Epub 2011 Jun 2. No abstract available.

    PubMed 21640398

  • Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, Muggia FM. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979 Nov;91(5):710-7. doi: 10.7326/0003-4819-91-5-710.

    PubMed 496103

  • Rivankar S. An overview of doxorubicin formulations in cancer therapy. J Cancer Res Ther. 2014 Oct-Dec;10(4):853-8. doi: 10.4103/0973-1482.139267.

    PubMed 25579518

  • Nielsen OS, Dombernowsky P, Mouridsen H, Daugaard S, Van Glabbeke M, Kirkpatrick A, Verweij J. Epirubicin is not Superior to Doxorubicin in the Treatment of Advanced Soft Tissue Sarcomas.The Experience of the EORTC Soft Tissue and Bone Sarcoma Group. Sarcoma. 2000;4(1-2):31-5. doi: 10.1155/S1357714X00000062.

    PubMed 18521432

  • Judson I, Radford JA, Harris M, Blay JY, van Hoesel Q, le Cesne A, van Oosterom AT, Clemons MJ, Kamby C, Hermans C, Whittaker J, Donato di Paola E, Verweij J, Nielsen S. Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2001 May;37(7):870-7. doi: 10.1016/s0959-8049(01)00050-8.

    PubMed 11313175

  • Bafaloukos D, Papadimitriou C, Linardou H, Aravantinos G, Papakostas P, Skarlos D, Kosmidis P, Fountzilas G, Gogas H, Kalofonos C, Dimopoulos AM. Combination of pegylated liposomal doxorubicin (PLD) and paclitaxel in patients with advanced soft tissue sarcoma: a phase II study of the Hellenic Cooperative Oncology Group. Br J Cancer. 2004 Nov 1;91(9):1639-44. doi: 10.1038/sj.bjc.6602148.

    PubMed 15494721

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing pegylated liposomal doxorubicin and pirarubicin in people with Progression-free Survival and Overall Survival, run by Peking University People's Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 19 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

progression-free survival (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03342300, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2020.

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