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 - Full Text View

Sponsor:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00753688

Purpose

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

Condition	Intervention	Phase
Sarcoma, Soft Tissue Soft Tissue Sarcoma	Drug: PAZOPANIB Drug: Placebo	Phase III

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

Resource links provided by NLM:

MedlinePlus related topics: Soft Tissue Sarcoma

Drug Information available for: Pazopanib

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Progression-free Survival (PFS) [ Time Frame: 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) ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Overall Survival (OS) [ Time Frame: From the date of randomization until 215 deaths (assessed for an average of 10 months) ] [ Designated as safety issue: No ]
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.
Number of Participants in the Indicated Categories for Overall Response Assessed by an Independent Radiologist and the Investigator [ Time Frame: From the start of treatment until disease progression (assessed for an average of 10 months) ] [ Designated as safety issue: No ]
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).
Time to Response Assessed by an Independent Radiologist and the Investigator [ Time Frame: From the date of randomization until the date of the first documented evidence of CR or PR (assessed for an average of 10 months) ] [ Designated as safety issue: No ]
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.
Duration of Response Assessed by the Independent Radiologist and the Investigator [ Time Frame: From the date of randomization until the date of the first documented evidence of CR or PR (assessed for an average of 10 months) ] [ Designated as safety issue: No ]
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.
PFS in the Indicated Histology Subgroups of Soft Tissue Sarcoma (STS) [ Time Frame: 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) ] [ Designated as safety issue: No ]
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.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [ Time Frame: 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 ] [ Designated as safety issue: No ]
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.
Change From Baseline in Heart Rate [ Time Frame: 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 ] [ Designated as safety issue: No ]
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.
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 [ Time Frame: From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks) ] [ Designated as safety issue: No ]
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.
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 [ Time Frame: From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks) ] [ Designated as safety issue: No ]
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.
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) [ Time Frame: 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) ] [ Designated as safety issue: No ]
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).

Enrollment:	369
Study Start Date:	October 2008
Estimated Study Completion Date:	May 2012
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: PLACEBO	Drug: Placebo placebo
Experimental: PAZOPANIB	Drug: PAZOPANIB experimental drug

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00753688

Show 75 Study Locations

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier:	NCT00753688 History of Changes
Obsolete Identifiers:	NCT00794521
Other Study ID Numbers:	VEG110727
Study First Received:	September 12, 2008
Results First Received:	November 17, 2011
Last Updated:	November 17, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:

metastatic soft-tissue sarcoma
pazopanib
placebo

Additional relevant MeSH terms:

Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on February 09, 2012