Pazopanib In Patients With Relapsed Or Refractory Soft Tissue Sarcoma

Sarcoma, Soft Tissue Clinical Trial

Official title:

Phase II Study of GW786034 in Patients With Relapsed or Refractory Soft Tissue Sarcoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00297258
• Other study ID #: VEG20002
• Status: Completed
• Phase: Phase 2
• First received: February 24, 2006
• Last updated: January 4, 2016
• Start date: November 2005
• Est. completion date: February 2014

Study information

• Verified date: December 2015
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00293449

Recruitment information / eligibility

• Status: Completed
• Enrollment: 148
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sarcoma
• Sarcoma, Soft Tissue

Intervention

Drug:
• pazopanib
oral tablet

Locations

Country	Name	City	State
Belgium	GSK Investigational Site	Bruxelles
Belgium	GSK Investigational Site	Leuven
France	GSK Investigational Site	Lyon cedex 03
France	GSK Investigational Site	Marseille
France	GSK Investigational Site	Paris Cedex 05
France	GSK Investigational Site	Villejuif
Hungary	GSK Investigational Site	Budapest
Netherlands	GSK Investigational Site	Groningen
Netherlands	GSK Investigational Site	Leiden
Netherlands	GSK Investigational Site	Rotterdam
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	Newcastle upon Tyne
United Kingdom	GSK Investigational Site	Sheffield

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Belgium,  France,  Hungary,  Netherlands,  United Kingdom, 

References & Publications (2)

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. — View Citation

Sleijfer S, Ray-Coquard I, Papai Z, Le Cesne A, Scurr M, Schöffski 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival at Week 12	Progression free survival at week 12 is the number of participants who had a complete response (CR, all detectable tumor had disappeared) or a partial response (PR, a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum) or stable disease (SD, no change) 12 weeks from start of therapy, per response evaluation criteria in solid tumors (RECIST v1.0). Clinical progression is progression of disease without documented radiological evidence. Progressive disease (PD), a >=20% increase in target lesions.	Week 12	No
Secondary	Overall Survival	Overall survival is defined as the time from start of therapy until death. Participants who were still alive at the time of analysis were censored.	Start of therapy until death (up to approximately 5 years)	No
Secondary	Progression Free Survival	Progression free survival is defined as the interval between the start of treatment and the earliest date of disease progression or death due to any cause. Assessments of progression were made by the investigator.	Start of therapy until progression (up to approximately 5 years)	No
Secondary	Overall Response	Overall response is the number of participants who had a best outcome of a complete response (CR, all detectable tumor had disappeared) or a partial response (PR, a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum) per response evaluation criteria in solid tumors (RECIST v1.0) at some point during the study. Progressive disease (PD), a >=20% increase in target lesions. Clinical progression is progression of disease without documented radiological evidence.	Baseline until either response or progression (up to approximately 5 years)	No