Clinical trial NCT00753688: Pazopanib Versus Placebo in Patients With Soft Tissue Sarcoma Whose Disease Has Progressed During or Following Prior Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sarcoma, Soft Tissue
Keywords: metastatic soft-tissue sarcoma
pazopanib
Soft Tissue Sarcoma
placebo
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-09-16
Enrollment: 369
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: 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)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From the date of randomization until 215 deaths (assessed for an average of 12 months)
measure: Number of Participants in the Indicated Categories for Overall Response Assessed by an Independent Radiologist and the Investigator
timeFrame: From the start of treatment until disease progression (assessed for an average of 10 months)
measure: Time to Response Assessed by an Independent Radiologist and the Investigator
timeFrame: From the date of randomization until the date of the first documented evidence of CR or PR (assessed for an average of 10 months)
measure: Duration of Response Assessed by the Independent Radiologist and the Investigator
timeFrame: From the date of randomization until the date of the first documented evidence of CR or PR (assessed for an average of 10 months)
measure: PFS in the Indicated Histology Subgroups of Soft Tissue Sarcoma (STS)
timeFrame: 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)
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: 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
measure: Change From Baseline in Heart Rate
timeFrame: 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
measure: 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
timeFrame: From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)
measure: 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
timeFrame: From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)
measure: 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)
timeFrame: 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)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Orange
country: United States
facility: GSK Investigational Site
state: California
city: Santa Monica
country: United States
facility: GSK Investigational Site
state: California
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Clevand
country: United States
facility: GSK Investigational Site
state: Ohio
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Randwick
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Woolloongabba
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Kurralta Park
country: Australia
facility: GSK Investigational Site
state: South Australia
city: Hobart
country: Australia
facility: GSK Investigational Site
state: Tasmania
city: Box Hill
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Nedlands
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Brussels
country: Belgium
facility: GSK Investigational Site
city: Brussels
country: Belgium
facility: GSK Investigational Site
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Liège
country: Belgium
facility: GSK Investigational Site
city: Herlev
country: Denmark
facility: GSK Investigational Site
city: Bordeaux cedex
country: France
facility: GSK Investigational Site
city: Lille
country: France
facility: GSK Investigational Site
city: Lyon Cedex 08
country: France
facility: GSK Investigational Site
city: Marseille cedex 5
country: France
facility: GSK Investigational Site
city: Paris Cedex 5
country: France
facility: GSK Investigational Site
city: Saint-Priest en Jarez
country: France
facility: GSK Investigational Site
city: Vandoeuvre-Les-Nancy
country: France
facility: GSK Investigational Site
city: Villejuif
country: France
facility: GSK Investigational Site
city: Heidelberg
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Mannheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Bad Saarow
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Koeln
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Napoli
country: Italy
facility: GSK Investigational Site
state: Campania
city: Roma
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Rozzano (MI)
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Candiolo (TO)
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Torino
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Terni
country: Italy
facility: GSK Investigational Site
state: Umbria
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Mie
country: Japan
facility: GSK Investigational Site
city: Okayama
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Daegu
country: Korea, Republic of
facility: GSK Investigational Site
city: Goyang-si, Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Groningen
country: Netherlands
facility: GSK Investigational Site
city: Leiden
country: Netherlands
facility: GSK Investigational Site
city: Nijmegen
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Palma de Mallorca
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Göteborg
country: Sweden
facility: GSK Investigational Site
city: Linköping
country: Sweden
facility: GSK Investigational Site
city: Lund
country: Sweden
facility: GSK Investigational Site
city: Umeå
country: Sweden
facility: GSK Investigational Site
city: Uppsala
country: Sweden
facility: GSK Investigational Site
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
state: Lancashire
city: Glasgow
country: United Kingdom
facility: GSK Investigational Site
city: Leeds
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Nottingham
country: United Kingdom
facility: GSK Investigational Site
city: Sheffield
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.