Soft tissue sarcoma (STS) MedDRA version: 15.1 Level: HLGT Classification code 10041299 Term: Soft tissue sarcomas System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: HLT Classification code 10041298 Term: Soft tissue sarcomas histology unspecified System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10075333 Term: Soft tis
Conditions
Interventions
Product Name: Pazopanib
Pharmaceutical Form: Tablet
INN or Proposed INN: PAZOPANIB
CAS Number: 444731-52-6
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 200-400
Sponsors
GWT-TUD GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The informed consent form must be signed before any study specific tests or procedures are done • Male or female patients aged 18 years and older at the first screening visit • Histologically confirmed diagnosis of advanced or metastatic nonadipocyte STS • Suitable for treatment with pazopanib in an in-label prescription • Patients with a life expectancy of at least 6 months • ECOG performance status 0-2 • Adequate organ function as given in Table 1 • For patients with previous anthracycline therapy a normal heart function needs to be documented with an LVEF of minimal 50% (echocardiogram or MUGA scan) • Patients must be willing and able to fill in the QoL questionnaires using a tablet PC • Ability to understand and follow study-related instructions • Confirmation of the subject's health insurance coverage prior to the first visit Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: Subjects are to be excluded from the study if they display any of the following criteria: • Pretreatment with pazopanib • Contraindications according to the local SmPC of Votrient® (see Appendix 1) Patients having to following STS specific Tumors: o adipocyte sarcoma including all subtypes o all rhabdomyo sarcoma, o Chondro sarcoma o Osteo sarcoma o Ewing-tumors, o Dermatofibrosarcoma protuberans o Inflammatory myofibroblastic sarcoma o Malignant mesotheliom o Mixed mesenchymal and epidermal tumors of the uterus. • Other malignant underlying diseases with the exception of the following: o Free of disease for at least three years o Completely resected, non-melanoma skin cancer o Successfully treated carcinoma in situ o Patients with metastases of the central nervous system (CNS) at screening, which are asymptomatic AND do not require treatment with steroids or enzyme-inducing anticonvulsant drugs o Patients with metastases of the CNS, which are already treated (operation and/or radiotherapy, radiosurgery or gamma-knife) • Major surgery or trauma within 28 days before the first dose of study medication and / or presence of a non-healing wound, fracture, or ulcer (procedures like insertion of an ureteral stent are not regarded as major surgery) • Clinical indications of an active bleeding or a bleeding diathesis • Known endobronchial lesions or lesions that infiltrate the large pulmonary artery • Hemoptysis of > 2.5 mL within eight weeks before the first dose of study drug • Existing uncontrolled infection Heart rate-corrected QT-time according to the Fridericia´s-formula (QTcF) = 450 ms in males and = 460 ms in females • History of one or more of the following cardiovascular diseases within the last 6 months: o Cardiac angioplasty or coronary stent o Myocardial infarction o Unstable angina pectoris o Coronary artery bypass surgery o Symptomatic peripheral arterial disease • Cardiac insufficiency NYHA functional class III or IV Poorly controlled hypertension defined as systolic blood pressure = 140 mmHg or diastolic blood pressure = 90 mmHg. (Note: Start or adjustment of antihypertensive medication prior to study entry is allowed. Blood pressure should in this case be be stable for at least 2 weeks and re-evaluated at least twice with a minimum distance of 1 hour. The average of all measurements must be <140/90 to allow inclusion of the patient). • History of cerebrovascular disease, including transient ischemic attacks (TIA), pulmonary embolism or untreated deep vein thrombosis within 6 months prior to study entry. Patients with deep vein thrombosis who have received therapeutic anticoagulation for a minimum of six weeks might be included in the study. • Clinically significant gastrointestinal changes that increase the risk of gastrointestinal bleeding, including (but not exclusively): o Active peptic ulceration o Known intraluminal metastases with a risk of bleeding o Inflammatory bowel disease (e.g. Morbus Crohn, Colitis ulcerosa) or other gastrointestinal disease with increased risk of perforation o A history of existing abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to study entry • Clinically significant gastrointestinal changes that may affect the absorption of the study drugs, including (but not exclusively): malabsorption or resection of the stomach or small intestine • Treatment with any of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Compare the overall quality of life (QoL) under treatment with pazopanib or physician-preferred chemotherapy after 9 weeks;Secondary Objective: Patient-reported outcomes (PROs) Clinical outcomes Predictors of toxicity in patients 60 years and older Safety parameters;Primary end point(s): The primary variable assessed in this study is the overall QoL measured by EORTC QLQ-C30 (sum score) after 9 weeks of treatment.;Timepoint(s) of evaluation of this end point: after 9 weeks of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Patient-reported outcomes (PROs) • Overall QoL and functional dimensions as well as symptoms, measured by EORTC QLQ-C30 in Week 1, 2, 3 compared to Week 7, 8, 9 • Pain measured by BPI-SF (baseline and Week 3, 6, 9) • Fatigue measured by MFI (baseline and Week 3, 6, 9) • Satisfaction with the tumor treatment measured by CTSQ (baseline and Week 9) • Anorexia/cachexia syndrome (ACS) measured by FAACT (baseline and Week 9) • Therapy-associated impairment and burden measured by the adapted MDASI (baseline and Week 3, 6, 9) • Individual subjective benefit assessment of the therapy by the patient using the time trade-off method (baseline and Week 9) Clinical outcomes • Progression free survival (PFS) • Overall survival (OS) • Objective response rate (ORR) • Clinical benefit rate (CBR) • Parameter determined by RECIST 1.1 Predictors of toxicity in patients 60 years and older • Predictors of toxicity according to Hurria et al. • Vulnerable Elderly Scale (VES-13) • Charlson Comorbidity Index Safety parameters Safety laboratory analyses (for details see Table 5), dose reductions and delay, AEs, concomitant medication;Timepoint(s) of evaluation of this end point: Patient-reported outcomes (PROs) -Overall QoL and functional dimensions as well as symptoms, measured by week 7, 8, 9 --BPI-SF (baseline and Week 3, 6, 9) -F- MFI (baseline and Week 3, 6, 9) - CTSQ (baseline and Week 9) -FAACT (baseline and Week 9) -Therapy-associated impairment and burden measured by the adapted MDASI (baseline and Week 3, 6, 9) -Individual subjective benefit assessment of the therapy by the patient using the time trade-off method (baseline and Week 9) Clinical outcomes (week 1,3,6,9) Safety parameters and dose reductions and delay, AEs, concomitant medication(week 1,3,6,9 (and during 2 years follow up everny 12 weeks) | — |
Countries
Germany, Switzerland
Contacts
Public ContactSponsor
GWT-TUD GmbH
Outcome results
None listed