E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced and relapsed angiosarcoma |
fortgeschrittene und rezidivierende Angiosarkome |
|
E.1.1.1 | Medical condition in easily understood language |
Malignant soft tissue tumour |
Bösartiger Weichteiltumor |
|
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 | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002481 |
E.1.2 | Term | Angiosarcoma stage 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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072814 |
E.1.2 | Term | Breast angiosarcoma metastatic |
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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072813 |
E.1.2 | Term | Breast angiosarcoma |
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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025223 |
E.1.2 | Term | Lymphangiosarcoma |
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 | 18.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10025224 |
E.1.2 | Term | Lymphangiosarcomas |
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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057700 |
E.1.2 | Term | Angiosarcoma non-metastatic |
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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002480 |
E.1.2 | Term | Angiosarcoma recurrent |
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 | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018827 |
E.1.2 | Term | Haemangiosarcoma |
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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072891 |
E.1.2 | Term | Skin angiosarcoma |
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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067388 |
E.1.2 | Term | Hepatic angiosarcoma |
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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002477 |
E.1.2 | Term | Angiosarcoma metastatic |
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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002476 |
E.1.2 | Term | Angiosarcoma |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
to evaluate progression free survival at 6 month (PFS-R) |
Rate des progessionsfreien Überlebens nach 6 Monaten (PFS-R) |
|
E.2.2 | Secondary objectives of the trial |
to evaluate response rate according to RECIST 1.1, overall survival and assessment of safety aspects |
das Gesamtüberleben, die Ansprechrate gemäß RECIST 1.1 und der Schweregrad der Nebenwirkungen bzw. Toxizität |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow-up.
Note: Procedures conducted as part of the subject’s routine clinical management (e.g., blood count, imaging studies) and obtained prior to signing informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol.
2. Age ≥ 18 years
3. Life expectancy > 3 months
4. Ability to swallow tablets
5. Histological confirmed angiosarcoma, primary and secondary angiosarcoma (e.g. radiation-induced or angiosarcoma in chronical lymphedema) are eligible.
6. Tumor must be locally advanced (unresectable) or metastatic. A progression must be documented within a 6-month period prior to screening.
7. ECOG performance status ≤ 2
8. At least one measurable skin lesion or one measurable radiological (CT or MRI) target lesion (RECIST 1.1)
9. Adequate organ system function as described in protocoll
10. A female is eligible to enter and participate in this study if she is either of non childbearing potential (defined in protocol) or childbearing potential with negativ pregnancy test within 2 weeks prior to the first dose of study drug and agrees to use adequate contraception (as defined in protocol) during the study and for 6 month after the last dose of study drug.
11. All sexually active male patients must agree to use adequate methods of birth control (see protocol) throughout the study and for 6 month after the last dose of study drug.
|
1. Vorhandensein einer schriftlichen Einwilligung des Patienten
2. Alter ≥ 18 Jahre
3. Lebenserwartung > 3 Monate
4. Fähigkeit Tabletten zu schlucken
5. Histologisch gesichertes Angiosarkom.
6. Lokal fortgeschrittene oder metastasierte Erkrankung mit einem Progress innerhalb der letzten 6 Monate vor Studieneinschluss
7. ECOG ≤ 2
8. Vorhandensein mindestens einer messbaren Hautmanifestation oder einer mit CT oder MRT messbaren Läsion (RECIST v1.1)
9. Adäquate Organfunktion:
Absolute Neutophilenzahl (ANC) ≥1.5 X 109/L
Hämoglobin ≥9 g/dL (5.6 mmol/L)
Thrombozyten ≥100 X 109/L
Prothrombin-Zeit (PT) oder INR ≤1.2 X obere Normalgrenze (ULN)
partielle Thromboplastinzeit (PTT) ≤ 1.2 X ULN
Gesamt-Bilirubin ≤ 1.5 X ULN
ASAT und ALAT ≤ 2.5 X ULN
Serumkreatinin ≤ 1.5 mg/dL (133 μmol/L)
wenn Serumkreatinin >1.5 mg/dL, dann kalkulierte glomeruläre Filtrationsrate (GFR) ≥ 50 mL/min
Protein/Kreatinin Verhältnis (UPC) < 1, wenn UPC ≥1, dann 24h-Urinprotein < 1
10. Gebärunfähigkeit oder negativer Schwangerschaftstest und adäquate Kontrazeption bei gebärfähigen Frauen bis 6 Monate nach Einnahme der letzten Studienmedikation
11. Vorhandensein einer adäquaten Kontrazeption bei zeugungsfähigen Männern bis 6 Monate nach Einnahme der letzten Studienmedikation
|
|
E.4 | Principal exclusion criteria |
1. Patients who need an active treatment for another malignant disease other than angiosarcoma
2. Prior treatment with a taxan within the last 12 months before study entry
3. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal sarcomatosis
4. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding
5. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
6. Presence of uncontrolled infection
7. QT prolongation interval (QTc) > 480 msecs
8. Clinically significant cardiovascular discorders within the past 6 months
9. Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer
10. Poorly controlled hypertension (see protocol)
11. Evidence of active bleeding or bleeding diathesis
12. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
13. Uncontrolled seizures, disorders of the CNS or psychiatric disorders which may put patient safety at risk, prevent giving informed consent or impact the patient's compliance with the use of study medication
14. Women who are pregnant or breast feeding
15. Patients who are not able or not willing to interrupt the intake of medications that are not allowed according to study protocol for at least 14 days before start of study medication and for the whole study period
16. Chemotherapy or radiotherapy within 14 days before start of study medication
17. Any ongoing toxicity from prior anti-cancer therapy that is > grade 1 and/or that is progressing in severity, except alopecia
Please note: Any treatment with Pazopanib before study entry is NOT allowed. |
1. Aktive Therapie für eine andere maligne Erkrankung als das Angiosarkom
2. Behandlung mit einem Taxan innerhalb der letzten 12 Monate vor Studieneinschluss
3. Vorhandensein von ZNS Metastasen oder leptomeningealen Sarkomatosen.
4. Klinisch signifikante gastrointestinale Störungen mit/ erhöhtem Risiko für gastrointestinale-Blutungen.
5. Klinisch signifikante gastrointestinale Störungen mit/ möglicher veränderter Absorption des Prüfpräparates.
6. Vorhandensein unkontrollierter Infektionen.
7.QT-Verlängerung im EKG, QTc > 480ms
8. Klinisch signifikante Herz-Kreislauf-Erkrankungen innerhalb der letzten 6 Monate vor Studieneinschluss,
9. „Großer“ operativer Eingriff innerhalb der letzten 28 Tage, nicht heilende Wunde oder Fraktur
10. Schlecht eingestellter arterieller Hypertonus.
11. Vorhandensein von massiver Blutung oder Blutungsneigung
12. Vorhandensein von endobronchialen Läsionen und/oder Läsionen in den Lungengefäßen
13. Nicht kontrollierte zerebrale Krampfanfälle, ZNS- oder psychiatrische Erkrankung, welche die Sicherheit des Patienten gefährdet, oder die Compliance beeinträchtigt.
14. Schwangere Frauen und stillende Mütter
15. Unfähigkeit oder fehlende Bereitschaft die Einnahme von den laut Prüfplan verbotenen Medikamenten für mindestens 14 Tage vor Gabe der ersten Studienmedikation und für die Dauer der Studie zu unterbrechen.
16. Chemotherapie oder Strahlentherapie 14 Tage vor der ersten Gabe der Studienmedikation
17. Anhaltende Toxizität von vorausgegangenen Anti-Krebs-Therapien die > Grad 1 und/oder fortschreitend im Schweregrad ist, außer Alopezie.
Hinweis: Jegliche Behandlung mit Pazopanib vor Studieneinschluss ist NICHT erlaubt. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
rate of progression free survival at 6 month (PFS-R) |
progressionsfreies Überleben nach 6 Monaten |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Overall survival (OS)
Response Rate (RR rate according to RECIST Version 1.1)
Toxicity (according to CTCAE, Version 4.0) |
Gesamt Überleben (OS)
Ansprechrate (RR gemäß RECIST Version 1.1)
Toxizitäten (gemäß CTCAE, Version 4.0)
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
during study is running |
während der laufenden klinischen Prüfung |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
|
Last Visit of the last subject (LVLS) |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |