Pazopanib Versus Placebo in Patients With Soft Tissue Sarcoma Whose Disease Has Progressed During or Following Prior Therapy (PALETTE)
15. august 2013 opdateret af: GlaxoSmithKline
A Randomized Double Blind Phase III Trial of Pazopanib Versus Placebo in Patients With Soft Tissue Sarcoma Whose Disease Has Progressed During or Following Prior Therapy
A randomized double blind phase III trial of Pazopanib versus placebo in patients with soft tissue sarcoma whose disease has progressed during or following prior therapy
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
369
Fase
- Fase 3
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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New South Wales
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Randwick, New South Wales, Australien, 2031
- GSK Investigational Site
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Queensland
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Woolloongabba, Queensland, Australien, 4102
- GSK Investigational Site
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South Australia
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Kurralta Park, South Australia, Australien, 5037
- GSK Investigational Site
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Tasmania
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Hobart, Tasmania, Australien, 7000
- GSK Investigational Site
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Victoria
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Box Hill, Victoria, Australien, 3128
- GSK Investigational Site
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Western Australia
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Nedlands, Western Australia, Australien, 6009
- GSK Investigational Site
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Brussels, Belgien, 1000
- GSK Investigational Site
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Brussels, Belgien, 1200
- GSK Investigational Site
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Gent, Belgien, 9000
- GSK Investigational Site
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Leuven, Belgien, 3000
- GSK Investigational Site
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Liège, Belgien, 4000
- GSK Investigational Site
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Herlev, Danmark, DK-2730
- GSK Investigational Site
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Glasgow, Det Forenede Kongerige, G12 0YN
- GSK Investigational Site
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Leeds, Det Forenede Kongerige, LS9 7TF
- GSK Investigational Site
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London, Det Forenede Kongerige, SW3 6JJ
- GSK Investigational Site
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Nottingham, Det Forenede Kongerige, NG5 1PB
- GSK Investigational Site
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Sheffield, Det Forenede Kongerige, S10 2SJ
- GSK Investigational Site
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Lancashire
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Manchester, Lancashire, Det Forenede Kongerige, M20 4BX
- GSK Investigational Site
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Alabama
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Birmingham, Alabama, Forenede Stater, 35243
- GSK Investigational Site
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California
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Los Angeles, California, Forenede Stater, 90048
- GSK Investigational Site
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Orange, California, Forenede Stater, 92868
- GSK Investigational Site
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Santa Monica, California, Forenede Stater, 90403
- GSK Investigational Site
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Illinois
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Chicago, Illinois, Forenede Stater, 60657
- GSK Investigational Site
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02114
- GSK Investigational Site
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Boston, Massachusetts, Forenede Stater, 02215
- GSK Investigational Site
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Minnesota
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Minneapolis, Minnesota, Forenede Stater, 55455
- GSK Investigational Site
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Ohio
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Clevand, Ohio, Forenede Stater, 44106
- GSK Investigational Site
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Pennsylvania
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Philadelphia, Pennsylvania, Forenede Stater, 19106
- GSK Investigational Site
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Bordeaux cedex, Frankrig, 33076
- GSK Investigational Site
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Lille, Frankrig, 59020
- GSK Investigational Site
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Lyon Cedex 08, Frankrig, 69373
- GSK Investigational Site
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Marseille cedex 5, Frankrig, 13385
- GSK Investigational Site
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Paris Cedex 5, Frankrig, 75248
- GSK Investigational Site
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Saint-Priest en Jarez, Frankrig, 42271
- GSK Investigational Site
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Vandoeuvre-Les-Nancy, Frankrig, 54511
- GSK Investigational Site
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Villejuif, Frankrig, 94805
- GSK Investigational Site
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Amsterdam, Holland, 1066 CX
- GSK Investigational Site
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Groningen, Holland, 9713 GZ
- GSK Investigational Site
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Leiden, Holland, 2300 RC
- GSK Investigational Site
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Nijmegen, Holland, 6525 GA
- GSK Investigational Site
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Rotterdam, Holland, 3075 EA
- GSK Investigational Site
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Campania
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Napoli, Campania, Italien, 80131
- GSK Investigational Site
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Lazio
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Roma, Lazio, Italien, 00144
- GSK Investigational Site
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Lombardia
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Milano, Lombardia, Italien, 20133
- GSK Investigational Site
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Milano, Lombardia, Italien, 20162
- GSK Investigational Site
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Rozzano (MI), Lombardia, Italien, 20089
- GSK Investigational Site
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Piemonte
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Candiolo (TO), Piemonte, Italien, 10060
- GSK Investigational Site
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Torino, Piemonte, Italien, 10153
- GSK Investigational Site
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Umbria
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Terni, Umbria, Italien, 05100
- GSK Investigational Site
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Aichi, Japan, 464-8681
- GSK Investigational Site
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Chiba, Japan, 260-8717
- GSK Investigational Site
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Fukuoka, Japan, 811-1395
- GSK Investigational Site
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Hokkaido, Japan, 003-0804
- GSK Investigational Site
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Mie, Japan, 514-8507
- GSK Investigational Site
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Okayama, Japan, 700-8558
- GSK Investigational Site
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Osaka, Japan, 540-0006
- GSK Investigational Site
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Osaka, Japan, 537-8511
- GSK Investigational Site
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Tokyo, Japan, 104-0045
- GSK Investigational Site
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Daegu, Korea, Republikken, 705-717
- GSK Investigational Site
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Goyang-si, Gyeonggi-do, Korea, Republikken, 410-769
- GSK Investigational Site
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Seoul, Korea, Republikken, 120-752
- GSK Investigational Site
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Seoul, Korea, Republikken, 138-736
- GSK Investigational Site
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Seoul, Korea, Republikken, 110-744
- GSK Investigational Site
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Seoul, Korea, Republikken, 135-710
- GSK Investigational Site
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Madrid, Spanien, 28041
- GSK Investigational Site
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Madrid, Spanien, 28040
- GSK Investigational Site
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Palma de Mallorca, Spanien, 07010
- GSK Investigational Site
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Valencia, Spanien, 46009
- GSK Investigational Site
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Göteborg, Sverige, SE413 45
- GSK Investigational Site
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Linköping, Sverige, SE-581 85
- GSK Investigational Site
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Lund, Sverige, SE-221 85
- GSK Investigational Site
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Umeå, Sverige, SE-901 85
- GSK Investigational Site
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Uppsala, Sverige, SE-751 85
- GSK Investigational Site
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Baden-Wuerttemberg
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Heidelberg, Baden-Wuerttemberg, Tyskland, 69120
- GSK Investigational Site
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Mannheim, Baden-Wuerttemberg, Tyskland, 68167
- GSK Investigational Site
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Brandenburg
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Bad Saarow, Brandenburg, Tyskland, 15526
- GSK Investigational Site
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Hessen
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Frankfurt, Hessen, Tyskland, 60590
- GSK Investigational Site
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Niedersachsen
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Hannover, Niedersachsen, Tyskland, 30625
- GSK Investigational Site
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Nordrhein-Westfalen
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Essen, Nordrhein-Westfalen, Tyskland, 45122
- GSK Investigational Site
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Koeln, Nordrhein-Westfalen, Tyskland, 50937
- GSK Investigational Site
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Sachsen
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Dresden, Sachsen, Tyskland, 01307
- GSK Investigational Site
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion/Exclusion Criteria:
- High or intermediate grade of soft tissue sarcoma; Low grade tumours allowed provided there is disease progression.
- Metastatic and measurable disease (RECIST);
- Subjects can have received maximum of 4 prior lines of systemic therapies (including up to 2 combination regimens) for advanced disease. (Neo) adjuvant/maintenance treatments are not counted for this criterion;
- Last dose of prior therapy can be given upto 14 days prior to start of study if all ongoing toxicity from prior anticancer therapy are grade 1 or resolved (except alopecia).
- Must have failed anthracycline-based therapy and available standard chemotherapies at the treating institution except if medically contraindicated or refused by patient;
- No treatment with anti-angiogenesis inhibitors;
- Age > 18 years
- WHO PS 0-1;
- No leptomeningeal or brain metastases, normal bone marrow, liver, renal and cardiac functions;
- No prior history of malignancies other than sarcoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix or breast or the patient has been free of any other malignancies for > 3 years)
- Adequate bone marrow function; adequate blood clotting results; adequate hepatic and renal function;
- No poorly controlled hypertension;
- Clinically normal cardiac function;
- No clinically significant gastrointestinal abnormalities including malabsorption syndrome, major resection of the stomach or small bowel that could affect the absorption of study drug, active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment.
- No cerebrovascular accidents 1
- No transient ischemic attack, deep vein thrombosis or pulmonary embolism within past six months;
- No active bleeding or bleeding diathesis;
- No hemoptysis within six weeks of study drug;
- No major surgery or trauma within 28 days of therapy treatment;
- Concomitant medication restriction;
- No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib
- Ability to swallow & retain oral medication
- Adequate contraception must be used;
- No Psychological familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed with the patient before randomization in the trial.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Placebo komparator: PLACEBO
matching placebo 800 mg once daily orally
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matching placebo 800 mg once daily orally
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Eksperimentel: PAZOPANIB
800 mg once daily orally
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800 mg once daily orally
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Progression-free Survival (PFS)
Tidsramme: From the date of randomization until the date of the first documented radiological progression or date of death from any cause, whichever came first (assessed for an average of 10 months)
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PFS was defined as the time interval between the date of randomization and the earliest date of either disease progression or death due to any cause.
The diagnosis of progression was based on tumor measurements, according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 criteria, by independent radiologic assessment.
The Kaplan-Meier method was used for PFS estimates.
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From the date of randomization until the date of the first documented radiological progression or date of death from any cause, whichever came first (assessed for an average of 10 months)
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Overall Survival (OS)
Tidsramme: From the date of randomization until 215 deaths (assessed for an average of 12 months)
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OS was defined as the time from the date of randomization to the date of death due to any cause.
The length of this interval was calculated as the date of death minus the date of randomization plus 1 day.
Participants who were alive at the time of analysis were censored at the date of last follow-up.
The interim OS analysis was conducted when 215 (77 percent [%]) of the 279 required death events had occurred in the study.
The Kaplan-Meier method was used for OS estimates.
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From the date of randomization until 215 deaths (assessed for an average of 12 months)
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Number of Participants in the Indicated Categories for Overall Response Assessed by an Independent Radiologist and the Investigator
Tidsramme: From the start of treatment until disease progression (assessed for an average of 10 months)
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Overall response is defined as the number of participants who had a complete response (CR) or a partial response (PR).
According to RECIST, Version 1.0: CR, disappearance of all lesions; PR, a >=30% decrease in the sum of the longest dimensions (LD) of the target lesions (TLs) taking as a reference the baseline sum LD; Progressive disease (PD), a >=20% increase in the sum of the LD of TLs, or the appearance of >=1 new lesion; Stable Disease (SD), neither PR nor PD, persistence of >=1 non-TL.
Participants with no follow-up radiological disease assessment were categorized as not evaluable (NE).
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From the start of treatment until disease progression (assessed for an average of 10 months)
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Time to Response Assessed by an Independent Radiologist and the Investigator
Tidsramme: From the date of randomization until the date of the first documented evidence of CR or PR (assessed for an average of 10 months)
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Time to response was defined as the time from the date of randomization until the date of first documented evidence of CR or PR (whichever status was recorded first).
The Kaplan-Meier method was used for time to response estimates.
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From the date of randomization until the date of the first documented evidence of CR or PR (assessed for an average of 10 months)
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Duration of Response Assessed by the Independent Radiologist and the Investigator
Tidsramme: From the date of randomization until the date of the first documented evidence of CR or PR (assessed for an average of 10 months)
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Duration of response was defined as the time from the date of the first documented evidence of CR or PR until the date of either the first documented sign of PD or death due to any cause.
Participants who neither died nor progressed were censored at the date of the last adequate radiologic assessment.
The Kaplan-Meier method was used for duration of response estimates.
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From the date of randomization until the date of the first documented evidence of CR or PR (assessed for an average of 10 months)
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PFS in the Indicated Histology Subgroups of Soft Tissue Sarcoma (STS)
Tidsramme: From the date of randomization until the date of the first documented progression or the date of death from any cause, whichever came first (assessed for an average of 10 months)
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PFS was defined as the time interval between the date of randomization and the earliest date of either disease progression or death due to any cause.
Participants were analyzed for PFS in histology subgroups of STS (as per the World Health Organization [WHO] classification, 2008): leiomyosarcoma (malignant cancer of smooth muscle), synovial sarcoma (cancer near the joints of the arm or leg), and other STS (without the tumor type of leiomyosarcoma or synovial sarcoma), based on independent review.The Kaplan-Meier method was used for PFS estimates.
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From the date of randomization until the date of the first documented progression or the date of death from any cause, whichever came first (assessed for an average of 10 months)
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Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Tidsramme: Baseline, Day 8, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 88, 96, and 104
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Change from baseline in on-therapy SBP and DBP was calculated as the values at the indicated time points (Day 8 and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 88, 96, and 104) minus the value at baseline.
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Baseline, Day 8, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 88, 96, and 104
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Change From Baseline in Heart Rate
Tidsramme: Baseline, Day 8, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 88, 96, and 104
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Change from baseline in on-therapy heart rate was calculated as the value at the indicated time points (Day 8 and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 88, 96, and 104) minus the value at baseline.
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Baseline, Day 8, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 88, 96, and 104
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Number of Participants With the Indicated Grade Shifts From Baseline Grade for Hemoglobin Level, Lymphocyte Count, White Blood Cell Count, Neutrophil Count, and Platelet Count
Tidsramme: From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)
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Shifts in hematology values by grade were summarized based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE Version 3.0).
Grade refers to the severity of the AE.
The CTCAE Version 3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline.
Participants with a missing baseline grade were assumed to have a baseline Grade of 0. Any increase in grade from baseline and shifts to Grade 3 (severe AE) and 4 (life-threatening or disabling AE) at any point in the study after baseline are reported.
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From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)
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Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin
Tidsramme: From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)
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Shifts in clinical chemistry values by grade were summarized based on the NCI CTCAE Version 3.0.
Participants with a missing baseline grade were assumed to have a baseline Grade of 0. Any increase in grade from baseline and shifts to Grade 3 and 4 at any point in the study after baseline are reported.
alkaline phosphatase, ALKP; alanine aminotransferase, ALT; aspartate aminotransferase, AST.
Hyper/hypoglycemia refers to high/low glucose; hyper/hypokalemia refers to high/low potassium; hyper/hyponatremia refers to high/low sodium.
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From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)
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Number of Participants With the Indicated Absolute Percent Change From Baseline (BL) in Left Ventricular Ejection Fraction (LVEF) at Any Time Post-BL (Worst Case On-therapy)
Tidsramme: Baseline (within 14 days of the first dose of study drug) and any time post-baseline until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)
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LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction and is used to determine cardiac function (based on the institutional lower limit of normal [LLN]).
LVEF was assessed at BL, Week 12, and every second scheduled visit thereafter until study drug discontinuation and end of treatment or as clinically indicated by using multi-gated acquisition scan (MUGA) or echocardiogram (ECHO).
Absolute change from BL was calculated as the on-study value minus the baseline value (LVEF is calculated as a percentage).
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Baseline (within 14 days of the first dose of study drug) and any time post-baseline until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Schoffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group; PALETTE study group. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012 May 19;379(9829):1879-86. doi: 10.1016/S0140-6736(12)60651-5. Epub 2012 May 16.
- Cesne AL, Bauer S, Demetri GD, Han G, Dezzani L, Ahmad Q, Blay JY, Judson I, Schoffski P, Aglietta M, Hohenberger P, Gelderblom H. Safety and efficacy of Pazopanib in advanced soft tissue sarcoma: PALETTE (EORTC 62072) subgroup analyses. BMC Cancer. 2019 Aug 13;19(1):794. doi: 10.1186/s12885-019-5988-3.
- Kawai A, Araki N, Hiraga H, Sugiura H, Matsumine A, Ozaki T, Ueda T, Ishii T, Esaki T, Machida M, Fukasawa N. A randomized, double-blind, placebo-controlled, Phase III study of pazopanib in patients with soft tissue sarcoma: results from the Japanese subgroup. Jpn J Clin Oncol. 2016 Mar;46(3):248-53. doi: 10.1093/jjco/hyv184. Epub 2016 Feb 10.
- Kasper B, Sleijfer S, Litiere S, Marreaud S, Verweij J, Hodge RA, Bauer S, Kerst JM, van der Graaf WTA. Long-term responders and survivors on pazopanib for advanced soft tissue sarcomas: subanalysis of two European Organisation for Research and Treatment of Cancer (EORTC) clinical trials 62043 and 62072. Ann Oncol. 2014 Mar;25(3):719-724. doi: 10.1093/annonc/mdt586. Epub 2014 Feb 6.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. oktober 2008
Primær færdiggørelse (Faktiske)
1. november 2010
Studieafslutning (Faktiske)
1. december 2012
Datoer for studieregistrering
Først indsendt
12. september 2008
Først indsendt, der opfyldte QC-kriterier
15. september 2008
Først opslået (Skøn)
16. september 2008
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
22. august 2013
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
15. august 2013
Sidst verificeret
1. august 2013
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- VEG110727
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .