- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03342300
Pegylated Liposomal Doxorubicin Versus Pirarubicin Plus Ifosfamide, Dacarbazine in Locally Advanced, Unresectable or Metastatic Soft-tissue Sarcoma (PDVPSTS)
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
Study Overview
Status
Conditions
Intervention / Treatment
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
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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-
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Beijing, China, 100044
- Peking University People's Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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).
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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.
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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).
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Another effort has been made to improve the toxicity profile of conventional anthracyclines is the development of novel anthracycline analogs,such as pirarubicin.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
progression-free survival
Time Frame: 12 weeks
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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.
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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
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objective response rate, ORR
Time Frame: 12 weeks
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objective response rate includes complete and partial responses as defined by RECIST version 1.1.
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12 weeks
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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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12 months
|
Collaborators and Investigators
Publications and helpful links
General 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.
- 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.
- 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.
- 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.
- 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.
- 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. Erratum In: Lancet. 2016 Jul 30;388(10043):464.
- 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.
- 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. Erratum In: Lancet Oncol. 2015 Sep;16(9):e427.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Poveda A, Lopez-Pousa A, Martin J, Del Muro JG, Bernabe R, Casado A, Balana C, Sanmartin O, Menendez MD, Escudero P, Cruz J, Belyakova E, Menendez D, Buesa JM. Phase II Clinical Trial With Pegylated Liposomal Doxorubicin (CAELYX(R)/Doxil(R)) and Quality of Life Evaluation (EORTC QLQ-C30) in Adult Patients With Advanced Soft Tissue Sarcomas: A study of the Spanish Group for Research in Sarcomas (GEIS). Sarcoma. 2005;9(3-4):127-32. doi: 10.1080/13577140500287024.
- Van Glabbeke M, Verweij J, Judson I, Nielsen OS; EORTC Soft Tissue and Bone Sarcoma Group. Progression-free rate as the principal end-point for phase II trials in soft-tissue sarcomas. Eur J Cancer. 2002 Mar;38(4):543-9. doi: 10.1016/s0959-8049(01)00398-7.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CBTRA-03
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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
Studies a U.S. FDA-regulated device product
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