Pazopanib Versus Placebo in Patients With Soft Tissue Sarcoma Whose Disease Has Progressed During or Following Prior Therapy

Sarcoma, Soft Tissue Clinical Trial

— PALETTE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00753688
• Other study ID #: VEG110727
• Status: Completed
• Phase: Phase 3
• First received: September 12, 2008
• Last updated: August 15, 2013
• Start date: October 2008
• Est. completion date: December 2012

Study information

• Verified date: August 2013
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Other known NCT identifiers

• NCT00794521

Recruitment information / eligibility

• Status: Completed
• Enrollment: 369
• Est. completion date: December 2012
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sarcoma
• Sarcoma, Soft Tissue

Intervention

Drug:
• PAZOPANIB
800 mg once daily orally
• Placebo
matching placebo 800 mg once daily orally

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Box Hill	Victoria
Australia	GSK Investigational Site	Hobart	Tasmania
Australia	GSK Investigational Site	Kurralta Park	South Australia
Australia	GSK Investigational Site	Nedlands	Western Australia
Australia	GSK Investigational Site	Randwick	New South Wales
Australia	GSK Investigational Site	Woolloongabba	Queensland
Belgium	GSK Investigational Site	Brussels
Belgium	GSK Investigational Site	Brussels
Belgium	GSK Investigational Site	Gent
Belgium	GSK Investigational Site	Leuven
Belgium	GSK Investigational Site	Liège
Denmark	GSK Investigational Site	Herlev
France	GSK Investigational Site	Bordeaux cedex
France	GSK Investigational Site	Lille
France	GSK Investigational Site	Lyon Cedex 08
France	GSK Investigational Site	Marseille cedex 5
France	GSK Investigational Site	Paris Cedex 5
France	GSK Investigational Site	Saint-Priest en Jarez
France	GSK Investigational Site	Vandoeuvre-Les-Nancy
France	GSK Investigational Site	Villejuif
Germany	GSK Investigational Site	Bad Saarow	Brandenburg
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Mannheim	Baden-Wuerttemberg
Italy	GSK Investigational Site	Candiolo (TO)	Piemonte
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Napoli	Campania
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Rozzano (MI)	Lombardia
Italy	GSK Investigational Site	Terni	Umbria
Italy	GSK Investigational Site	Torino	Piemonte
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Mie
Japan	GSK Investigational Site	Okayama
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Goyang-si, Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Netherlands	GSK Investigational Site	Amsterdam
Netherlands	GSK Investigational Site	Groningen
Netherlands	GSK Investigational Site	Leiden
Netherlands	GSK Investigational Site	Nijmegen
Netherlands	GSK Investigational Site	Rotterdam
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Palma de Mallorca
Spain	GSK Investigational Site	Valencia
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Linköping
Sweden	GSK Investigational Site	Lund
Sweden	GSK Investigational Site	Umeå
Sweden	GSK Investigational Site	Uppsala
United Kingdom	GSK Investigational Site	Glasgow
United Kingdom	GSK Investigational Site	Leeds
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Manchester	Lancashire
United Kingdom	GSK Investigational Site	Nottingham
United Kingdom	GSK Investigational Site	Sheffield
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Clevand	Ohio
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Minneapolis	Minnesota
United States	GSK Investigational Site	Orange	California
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Denmark,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Spain,  Sweden,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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)	No
Secondary	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.	From the date of randomization until 215 deaths (assessed for an average of 12 months)	No
Secondary	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).	From the start of treatment until disease progression (assessed for an average of 10 months)	No
Secondary	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.	From the date of randomization until the date of the first documented evidence of CR or PR (assessed for an average of 10 months)	No
Secondary	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.	From the date of randomization until the date of the first documented evidence of CR or PR (assessed for an average of 10 months)	No
Secondary	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.	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)	No
Secondary	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.	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	No
Secondary	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.	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	No
Secondary	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.	From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)	No
Secondary	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.	From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)	No
Secondary	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).	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)	No