Clinical trial NCT00297258: Pazopanib In Patients With Relapsed Or Refractory Soft Tissue Sarcoma
Official title: Phase II Study of GW786034 in Patients With Relapsed or Refractory Soft Tissue Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoma, Soft Tissue
Keywords: Sarcoma
Synovial sarcoma
Pazopanib(GW786034)
Adipocytic tumors
Leiomyosarcoma
Phase II
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-02-28
Enrollment: 148
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the activity and tolerability of pazopanib in subjects with advanced and/or metastatic soft tissue sarcoma who have relapsed following standard therapies or for whom no standard therapy exists and to characterize the pharmacokinetics of pazopanib in this subject population.


Eligibility criteria: Inclusion Criteria:

* Histological evidence of high or intermediate grade malignant soft tissue sarcoma, or cytological evidence in case of presence of multiple metastases. List of eligible and ineligible tumours are included in the protocol.
* Formalin fixed paraffin embedded tumour blocks and representative H/E (haematoxylin/eosin) slides must be available for histological central review. Histological central review is not required before treatment start but is mandatory within 3 months of registration. Local histopathological diagnosis will be accepted for entry into the study.
* Presence of measurable disease (according to RECIST criteria).
* Relapsed or refractory disease incurable by surgery or radiotherapy.
* Evidence of objective progression within the last 6 months (RECIST) documented by measurements of disease,
* Patients must either not be eligible for chemotherapy (for instance because of age, or because of a biological condition, or because of patient-refusal) or must have received no more than one combination or two single agents chemotherapy regimen for advanced disease; (neo) adjuvant therapy is not counted towards this requirement.
* At least 18 years of age
* WHO performance status 0 or 1
* Adequate bone marrow function
* Adequate hepatic function
* Adequate renal function
* PT / PTT less than 1.2 x UNL.
* LVEF above the lower limit of normal for the institution, based on ECHO or MUGA
* Able to swallow and retain oral medication
* Women should not be of childbearing potential and agree to use contraceptive methods (Oral contraceptives are not allowed).
* Absence of any serious and/or unstable pre-existing medical, psychiatric or other condition (including lab abnormality) that could interfere with patient safety or obtaining informed consent.
* Absence of any 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 registration in the trial.
* Written informed consent is given according to ICH/GCP, and national/local regulations before patient registration/randomization.

Exclusion Criteria:

* history of leptomeningeal or brain metastases
* history of malignancies other than sarcoma (except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or the patient has been free of any other malignancies for greater than 3 years).
* Class II, III or IV heart failure (NYHA classification). A patient who has a history of class II heart failure and is asymptomatic on treatment may be considered eligible.
* Arterial or venous thrombosis, myocardial infarction, unstable angina, cardiac angioplasty or stenting within the last 3 months
* Uncontrolled or poorly controlled hypertension. Initiation or adjustment of BP medications is permitted prior to study entry, provided that patient has 3 consecutive BP readings less than 150 / 90 mm Hg each separated by a minimum of 24 hrs. These readings need to be collected prior to registration in the study.
* Women of childbearing potential, who are pregnant (negative serum pregnancy test at entry) or lactating.
* Therapeutic dose warfarin. Low molecular weight heparin and prophylactic low dose warfarin are permitted. PT/INR and PPT must meet the above inclusion criteria.
* Concurrent therapy with any specifically prohibited medication or requirement for using any of these medications during treatment with pazopanib
* Major surgery, hormonal therapy (other than replacement), chemotherapy or radiotherapy, immunotherapy or other investigational agent within the last 28 days and/or not recovered from prior therapy within the last 28 days. Use of erythropoietin is considered supportive care and is permitted. The patient should have recovered from prior surgery and have no open wounds.
* History of malabsorption syndrome, disease significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect absorption, distribution, metabolism or excretion of study drugs. No unresolved bowel obstruction or diarrhea.

Primary outcomes:
measure: Progression Free Survival at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Overall Survival
timeFrame: Start of therapy until death (up to approximately 5 years)
measure: Progression Free Survival
timeFrame: Start of therapy until progression (up to approximately 5 years)
measure: Overall Response
timeFrame: Baseline until either response or progression (up to approximately 5 years)
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Lyon cedex 03
country: France
facility: GSK Investigational Site
city: Marseille
country: France
facility: GSK Investigational Site
city: Paris Cedex 05
country: France
facility: GSK Investigational Site
city: Villejuif
country: France
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Groningen
country: Netherlands
facility: GSK Investigational Site
city: Leiden
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
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: Newcastle upon Tyne
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: Sleijfer S, Ray-Coquard I, Papai Z, Le Cesne A, Scurr M, Schoffski P, Collin F, Pandite L, Marreaud S, De Brauwer A, van Glabbeke M, Verweij J, Blay JY. Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043). J Clin Oncol. 2009 Jul 1;27(19):3126-32. doi: 10.1200/JCO.2008.21.3223. Epub 2009 May 18.
citation: Sleijfer S, Gorlia T, Lamers C, Burger H, Blay JY, Le Cesne A, Scurr M, Collin F, Pandite L, Marreaud S, Hohenberger P. Cytokine and angiogenic factors associated with efficacy and toxicity of pazopanib in advanced soft-tissue sarcoma: an EORTC-STBSG study. Br J Cancer. 2012 Aug 7;107(4):639-45. doi: 10.1038/bjc.2012.328. Epub 2012 Jul 17.
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.