| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Soft tissue sarcoma (STS) |
| Weichgewebesarkome |
|
| E.1.1.1 | Medical condition in easily understood language |
| tumore in connective tissue |
| Tumore im Binde -und Stützgewebe |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 15.1 |
| E.1.2 | Level | HLGT |
| E.1.2 | Classification code | 10041299 |
| E.1.2 | Term | Soft tissue sarcomas |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10041298 |
| E.1.2 | Term | Soft tissue sarcomas histology unspecified |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10075333 |
| E.1.2 | Term | Soft tissue sarcoma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
• Compare the overall quality of life (QoL) under treatment with
pazopanib or physician-preferred chemotherapy after 9 weeks |
Allgemeine Lebensqualität (LQ) nach 9 Wochen, erhoben mit dem
Summenwert des EORTC QLQ-C30 Fragebogens |
|
| E.2.2 | Secondary objectives of the trial |
Patient-reported outcomes (PROs)
Clinical outcomes
Predictors of toxicity in patients 60 years and older
Safety parameters |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 |
Unterzeichnete Einwilligungserklärung
• Männliche oder weibliche Patienten ab 18 Jahre (inklusive)
• Histologisch bestätigte Diagnose einer fortgeschrittenen oder
metastasierten, nicht-adipozytären Sarkomerkrankung des
Weichgewebes
• Geeignet für die In-Label-Behandlung mit Pazopanib
• Arzteingeschätzte Lebenserwartung mindestens 6 Monate
• ECOG performance Status 0-2
• Adäquate Organfunktion
• Für Patienten mit vorausgegangener Anthracyclin-Therapie muss
eine normale Herzfunktion dokumentiert sein (linksventrikuläre
Auswurffraktion mindestens 50%)
• Bereitwilligkeit und Fähigkeit des Patienten, Fragebögen mit Hilfe
eines Tablet-PCs zu beantworten
• Fähigkeit, studienbezogenen Instruktionen zu folgen
• Bestehende Krankenversicherung des Patienten |
|
| E.4 | Principal 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 anti-neoplastic therapies:
o Irradiation or tumor embolization within 14 days prior to the first
dose of study drug
o Chemotherapy, immunotherapy, biological therapy, study
medication or hormonal therapy within 14 days or five half-lives of
substance (whichever is longer) prior to the first dose of study drug
• If the discontinuation of prohibited medication (see Section 6.9) at
least 14 days or five half-lives of substance (whichever is longer) prior
to the first dose of pazopanib is medically not acceptable or refused by
the patient
• A history of hypersensitivity to any of the study drugs or their
ingredients or to drugs with similar chemical structure
• Addiction or other diseases that preclude the patient from
appropriately assessing the nature and scope as well as possible
consequences of the clinical trial
• Pregnant or breast-feeding women
• Women of childbearing potential unless women who meet the
following criteria:
o Post-menopausal (12 months natural amenorrhea or 6 months
amenorrhea with serum FSH > 40 U / ml)
o Postoperatively (six weeks after bilateral ovariectomy with or
without hysterectomy)
o Regular and correct use of a contraceptive method with error rate
<1% per year such as implants, depot injections, oral contraceptives or
intrauterine devices
o Sexual abstinence
o Vasectomy of the partner
• Men of sexual activity with women of childbearing potential who are
not willing to use an effective barrier method |
Vorausgegangene Behandlung mit Pazopanib
• Kontraindikationen gemäß Fachinformation von Votrient®
• Andere Krebserkrankungen mit folgenden Ausnahmen
o Krankheitsfreiheit innerhalb der letzten drei Jahre
o Vollständig entfernter, nicht bösartiger Hautkrebs
o Erfolgreich behandeltes Karzinom in situ
o Patienten mit Metastasen im Zentralnervensystem (ZNS) zum
Zeitpunkt des Screenings, die asymptomatisch sind UND keiner
Behandlung mit Steroiden oder enzyminduzierenden Antikonvulsiva
bedürfen
o Patienten mit Metastasen im ZNS, die bereits behandelt wurden
(Operation, Radiotherapie etc.)
• Schwere Operation oder Trauma innerhalb der letzten 28 Tage
und/oder Vorhandensein einer nichtheilenden Wunde, Fraktur oder
eines Geschwürs
• Klinische Zeichen einer aktiven Blutung oder Blutungsbereitschaft
• Bekannte endobronchiale Läsionen oder Infiltrate der großen
Pulmonalarterie
• Hämoptyse von > 2.5 ml innerhalb der letzten 8 Wochen
• Vorliegende unkontrollierte Infektion
• QTcF ≥ 450 ms bei Männern oder ≥ 460 ms bei Frauen
• Historie von mindestens einer der folgenden kardiovaskulären
Krankheiten innerhalb der letzten 6 Monate:
o kardiale Angioplastie oder koronarer Stent
o Herzinfarkt
o Instabile Angina pectoris
o Bypass der Koronararterie
o Symptomatische periphere Arterienerkrankung
Herzinsuffizienz NYHA Klasse III oder IV
• Schlecht kontrollierter Bluthochdruck (systolischer Blutdruck ≥ 140
mmHg oder diastolischer Blutdruck ≥ 90 mmHg)
• Historie einer zerebrovaskulären Erkrankung einschließlich
vorübergehende Durchblutungsstörung, Lungenembolie oder
unbehandelte tiefe Venenthrombose in den letzten 6 Monaten.
Patienten, die zur Behandlung der tiefen Venenthrombose für
mindestens 6 Wochen Antikoagulantien erhalten haben, dürfen
eingeschlossen werden
• Klinisch relevante gastrointestinale Veränderungen mit
gesteigertem Risiko einer gastrointestinalen Blutung
• Klinisch relevante gastrointestinale Veränderungen, die die
Resorption der Studienmedikamente beeinflussen könnten
• Behandlung mit einer der folgenden anti-neoplastischen Therapien:
o Bestrahlung oder Tumorembolisation innerhalb der letzten 14 Tage
o Chemotherapie, Immuntherapie, biologische Therapie,
Studienmedikation oder hormonelle Therapie innerhalb der letzten 14
Tage oder 5 Halbwertszeiten der Substanz vor erster Gabe der
Studienmedikation
• Abbruch der Behandlung mit nicht zulässigen Begleitmedikationen
mindestens 14 Tage oder 5 Halbwertszeiten der Substanz vor der
ersten Gabe der Studienmedikation ist medizinisch nicht vertretbar
oder wird vom Patienten zurückgewiesen
Hypersensibilität gegenüber Medikamenten oder deren
Inhaltsstoffen oder gegenüber Substanzen mit chemisch ähnlicher
Struktur
• Sucht oder eine andere Erkrankung, die ausschließt, dass der
Patient den Zweck und die Risiken der klinischen Studie einschätzen
kann
• Schwangere oder stillende Frauen
• Gebärfähige Frauen sofern nicht die folgenden Voraussetzungen
erfüllt sind:
o Postmenopausal (12 Monate natürliche Amenorrhö oder 6 Monate
Amenorrhö mit FSH im Serum > 40 U / ml)
o Postoperativ (6 Wochen nach bilateraler Ovariektomie mit oder
ohne Hysterektomie)
o Regelmäßige und korrekte Verwendung einer kontrazeptiven
Methode mit einer Fehlerrate von < 1% pro Jahr wie z.B. Implantate,
Depotinjektionen, orale Kontrazeptiva oder Intrauterinpessar
o Sexuelle Abstinenz
o Vasektomie des Partners
• Männer, die mit gebärfähigen Frauen sexuell aktiv sind und nicht
bereit sind eine wirksame Barrieremethode zu verwenden während und
bis zu 3 Monate nach Ende der Studienmedikation |
|
| E.5 End points |
| E.5.1 | 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. |
Vergleich der Lebensqualität nach 9 Wochen Behandlung mit
Pazopanib oder vom behandelnden Arzt gewählter Chemotherapie |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| after 9 weeks of treatment. |
| nach 9 Wochen |
|
| E.5.2 | 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 |
Vergleich:
-der Lebensqualität unter Behandlung mit Pazopanib oder vom
behandelnden Arzt gewählter Chemotherapie dreimal je in Zyklus 1
und 3 (Woche 1, 2, 3 und 7, 8, 9)
-der beiden Behandlungsgruppen in Bezug auf Schmerzen als ein
Hauptsymptom für Weichgewebssarkom
-der beiden Behandlungsgruppen in Bezug auf Erschöpfung und deren
verschiedene Kategorien (physisch, mental, kognitiv, emotional)
- der beiden Behandlungsgruppen in Bezug auf Anorexie/Kachexie als
Marker für gesundheitsbezogene Lebensqualität
- der beiden Behandlungsgruppen in Bezug auf die Zufriedenheit mit
der Tumorbehandlung
und Untersuchung des Zusammenhangs der Lebensqualität mit
Kriterien des Ansprechens auf die Therapie (RECIST 1.1, if feasible)
|
|
| E.5.2.1 | 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) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Yes |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| End of the trail is the study report in Q1/2023 |
| Das Studienende ist durch den Studienreport definiert (Q1/2023) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
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