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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00753688




Registration number
NCT00753688
Ethics application status
Date submitted
12/09/2008
Date registered
16/09/2008
Date last updated
22/08/2013

Titles & IDs
Public title
Pazopanib Versus Placebo in Patients With Soft Tissue Sarcoma Whose Disease Has Progressed During or Following Prior Therapy
Scientific 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
Secondary ID [1] 0 0
VEG110727
Universal Trial Number (UTN)
Trial acronym
PALETTE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sarcoma, Soft Tissue 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PAZOPANIB
Treatment: Drugs - Placebo

Placebo Comparator: PLACEBO - matching placebo 800 mg once daily orally

Experimental: PAZOPANIB - 800 mg once daily orally


Treatment: Drugs: PAZOPANIB
800 mg once daily orally

Treatment: Drugs: Placebo
matching placebo 800 mg once daily orally

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) - 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.
Timepoint [1] 0 0
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 outcome [1] 0 0
Overall Survival (OS) - 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.
Timepoint [1] 0 0
From the date of randomization until 215 deaths (assessed for an average of 12 months)
Secondary outcome [2] 0 0
Number of Participants in the Indicated Categories for Overall Response Assessed by an Independent Radiologist and the Investigator - 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).
Timepoint [2] 0 0
From the start of treatment until disease progression (assessed for an average of 10 months)
Secondary outcome [3] 0 0
Time to Response Assessed by an Independent Radiologist and the Investigator - 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.
Timepoint [3] 0 0
From the date of randomization until the date of the first documented evidence of CR or PR (assessed for an average of 10 months)
Secondary outcome [4] 0 0
Duration of Response Assessed by the Independent Radiologist and the Investigator - 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.
Timepoint [4] 0 0
From the date of randomization until the date of the first documented evidence of CR or PR (assessed for an average of 10 months)
Secondary outcome [5] 0 0
PFS in the Indicated Histology Subgroups of Soft Tissue Sarcoma (STS) - 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.
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) - 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.
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
Change From Baseline in Heart Rate - 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.
Timepoint [7] 0 0
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
Secondary outcome [8] 0 0
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 - 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.
Timepoint [8] 0 0
From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)
Secondary outcome [9] 0 0
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 - 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.
Timepoint [9] 0 0
From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)
Secondary outcome [10] 0 0
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) - 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).
Timepoint [10] 0 0
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)

Eligibility
Key inclusion criteria
Inclusion/
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment hospital [2] 0 0
GSK Investigational Site - Woolloongabba
Recruitment hospital [3] 0 0
GSK Investigational Site - Kurralta Park
Recruitment hospital [4] 0 0
GSK Investigational Site - Hobart
Recruitment hospital [5] 0 0
GSK Investigational Site - Box Hill
Recruitment hospital [6] 0 0
GSK Investigational Site - Nedlands
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [4] 0 0
7000 - Hobart
Recruitment postcode(s) [5] 0 0
3128 - Box Hill
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
Belgium
State/province [8] 0 0
Brussels
Country [9] 0 0
Belgium
State/province [9] 0 0
Gent
Country [10] 0 0
Belgium
State/province [10] 0 0
Leuven
Country [11] 0 0
Belgium
State/province [11] 0 0
Liège
Country [12] 0 0
Denmark
State/province [12] 0 0
Herlev
Country [13] 0 0
France
State/province [13] 0 0
Bordeaux cedex
Country [14] 0 0
France
State/province [14] 0 0
Lille
Country [15] 0 0
France
State/province [15] 0 0
Lyon Cedex 08
Country [16] 0 0
France
State/province [16] 0 0
Marseille cedex 5
Country [17] 0 0
France
State/province [17] 0 0
Paris Cedex 5
Country [18] 0 0
France
State/province [18] 0 0
Saint-Priest en Jarez
Country [19] 0 0
France
State/province [19] 0 0
Vandoeuvre-Les-Nancy
Country [20] 0 0
France
State/province [20] 0 0
Villejuif
Country [21] 0 0
Germany
State/province [21] 0 0
Baden-Wuerttemberg
Country [22] 0 0
Germany
State/province [22] 0 0
Brandenburg
Country [23] 0 0
Germany
State/province [23] 0 0
Hessen
Country [24] 0 0
Germany
State/province [24] 0 0
Niedersachsen
Country [25] 0 0
Germany
State/province [25] 0 0
Nordrhein-Westfalen
Country [26] 0 0
Germany
State/province [26] 0 0
Sachsen
Country [27] 0 0
Italy
State/province [27] 0 0
Campania
Country [28] 0 0
Italy
State/province [28] 0 0
Lazio
Country [29] 0 0
Italy
State/province [29] 0 0
Lombardia
Country [30] 0 0
Italy
State/province [30] 0 0
Piemonte
Country [31] 0 0
Italy
State/province [31] 0 0
Umbria
Country [32] 0 0
Japan
State/province [32] 0 0
Aichi
Country [33] 0 0
Japan
State/province [33] 0 0
Chiba
Country [34] 0 0
Japan
State/province [34] 0 0
Fukuoka
Country [35] 0 0
Japan
State/province [35] 0 0
Hokkaido
Country [36] 0 0
Japan
State/province [36] 0 0
Mie
Country [37] 0 0
Japan
State/province [37] 0 0
Okayama
Country [38] 0 0
Japan
State/province [38] 0 0
Osaka
Country [39] 0 0
Japan
State/province [39] 0 0
Tokyo
Country [40] 0 0
Korea, Republic of
State/province [40] 0 0
Daegu
Country [41] 0 0
Korea, Republic of
State/province [41] 0 0
Goyang-si, Gyeonggi-do
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Seoul
Country [43] 0 0
Netherlands
State/province [43] 0 0
Amsterdam
Country [44] 0 0
Netherlands
State/province [44] 0 0
Groningen
Country [45] 0 0
Netherlands
State/province [45] 0 0
Leiden
Country [46] 0 0
Netherlands
State/province [46] 0 0
Nijmegen
Country [47] 0 0
Netherlands
State/province [47] 0 0
Rotterdam
Country [48] 0 0
Spain
State/province [48] 0 0
Madrid
Country [49] 0 0
Spain
State/province [49] 0 0
Palma de Mallorca
Country [50] 0 0
Spain
State/province [50] 0 0
Valencia
Country [51] 0 0
Sweden
State/province [51] 0 0
Göteborg
Country [52] 0 0
Sweden
State/province [52] 0 0
Linköping
Country [53] 0 0
Sweden
State/province [53] 0 0
Lund
Country [54] 0 0
Sweden
State/province [54] 0 0
Umeå
Country [55] 0 0
Sweden
State/province [55] 0 0
Uppsala
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Lancashire
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Glasgow
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Leeds
Country [59] 0 0
United Kingdom
State/province [59] 0 0
London
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Nottingham
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/show/NCT00753688
Trial related presentations / publications
van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Schöffski 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.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications