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SNCTP000003669 | NCT04212026 | BASEC2019-02408

SAKK 44/19: Behandlung von fortgeschrittenem Bauchspeicheldrüsenkrebs durch irreversible Elektroporation (Zerstörung durch elektrischen Strom) einer Lebermetastase, gefolgt von einer Immuntherapie mit Nivolumab: eine multizentrische, einarmige Phase-II-Studie (PDAC-IRE)

Base di dati: BASEC (Importata da 24.11.2020), WHO (Importata da 22.11.2020)
Cambiato: 15.11.2020
Categoria di malattie: Cancro del pancreas

Descrizione riassuntiva della sperimentazione (Fonte di dati: BASEC)

In dieser Studie wird eine neue Methode zur Behandlung von Patienten mit Bauchspeicheldrüsenkrebs (Pankreaskarzinom) und mehreren Metastasen in der Leber untersucht. Bei den Studienteilnehmenden wird eine Metastase in der Leber mit einem speziellen Verfahren, der IRreversiblen Elektroporation (IRE) zerstört. Anschliessend erhalten sie den Wirkstoff Nivolumab. Dieser gehört zur Medikament Gruppe der sogenannten «Checkpoint-Inhibitoren» – diese Medikamente erhöhen die Anzahl und Aktivität der Immunzellen, welche die Krebszellen angreifen. Bisher konnte nicht nachgewiesen werden, dass Nivolumab als alleinige Therapie bei Bauchspeicheldrüsenkrebs wirkt. Wir erhoffen uns aber, dass die IRE in der Leber eine Entzündungsreaktion mit Aktivierung des Immunsystems auslöst, die dazu führt, dass Nivolumab seine Wirkung entfalten kann und dadurch die Lebermetastasen und der Bauchspeicheldrüsenkrebs vom Immunsystem angegriffen werden.

Malattie studiate (Fonte di dati: BASEC)

fortgeschrittener Bauchspeicheldrüsenkrebs mit Lebermetastasen

Health conditions (Fonte di dati: WHO)

Metastatic Pancreatic Cancer

Malattia rara (Fonte di dati: BASEC)

No

Interventi esaminati (p. es. medicamento, terapia, campagna) (Fonte di dati: BASEC)

Bei den Studienteilnehmenden wird eine Metastase in der Leber mit einem speziellen Verfahren, der irreversiblen Elektroporation (IRE) zerstört. Anschliessend werden die Teilnehmenden mit dem Wirkstoff Nivolumab behandelt

Interventions (Fonte di dati: WHO)

Drug: Nivolumab

Criteri per la partecipazione alla sperimentazione (Fonte di dati: BASEC)

An der Studie können Personen teilnehmen, die über 18 Jahre alt und an Bauchspeicheldrüsenkrebs mit mindestens drei Metastasen in der Leber erkrankt sind. Zwei der Metastasen müssen in der Leber so liegen, dass sie für die Entnahme von Tumormaterial (Biopsie) durch die Haut erreicht werden können. Mindestens eine dieser beiden Metastasen muss im Durchmesser 1-4 cm gross sein, damit eine IRE sicher durchgeführt werden kann. Bei den Studienteilnehmenden muss bereits eine Standard-Chemotherapie zur Behandlung des Bauchspeicheldrüsenkrebses durchgeführt worden sein. Die Kontroll-Computertomographie/MRI muss innert 21 Tagen vor Studien-Einschluss durchgeführt worden sein. Der Allgemeinzustand der Teilnehmenden sollte gut und der Verlauf der Tumorkrankheit stabil sein. Frauen, die schwanger werden können, und Männer, die zeugungsfähig sind, müssen sich verpflichten, während der Studie und bis sieben Monate nach der letzten Gabe des Studienmedikaments nicht schwanger zu werden resp. kein Kind zu zeugen oder Spermien zu spenden.

Criteri di esclusione (Fonte di dati: BASEC)

Personen, bei denen eine nicht-kontrollierbare Aszites (Bauchwassersucht) vorliegt, können nicht an der Studie teilnehmen. Ebenfalls von der Studie ausgeschlossen sind Personen, die gegenwärtig gegen Krebs behandelt werden oder bei denen erst vor kurzer Zeit eine Krebstherapie durchgeführt wurde (inklusive Strahlenbehandlung, Behandlung mit Checkpoint-Inhibitoren oder experimentellen Wirkstoffen) – einzige Ausnahme ist die Chemotherapie gegen Bauchspeicheldrüsenkrebs. Auch nicht an der Studie teilnehmen können Personen, die unter schweren anderen Krankheiten leiden (z.B. Herz- oder Leberkrankheit) oder die mit Medikamenten zur Unterdrückung des Immunsystems behandelt werden. Personen, die Medikamente zur Blutverdünnung einnehmen müssen (mit Ausnahme von Aspirin in niedriger Dosierung) und bei denen diese Medikamente für die IRE und die Biopsien nicht abgesetzt werden können, können an der Studie ebenfalls nicht teilnehmen. Schwangere und stillende Frauen sind von der Studie ausgeschlossen.

Inclusion/Exclusion Criteria (Fonte di dati: WHO)


Inclusion Criteria:

- Written informed consent according to Swiss law and ICH GCP E6(R2) regulations before
registration and prior to any trial specific procedures.

- Pathologically proven PDAC with liver metastases either by histology or cytology.

- At least three liver metastases, measurable per RECIST v 1.1, of which at least two
are percutaneously accessible lesions for repeat biopsy, while one of the biopsied
lesions will be treated with IRE. The lesion amenable to IRE treatment must have a
diameter of 1-4 cm;

- At least stable disease after the completion of 10-18 weeks of first line standard
chemotherapy (either (m)FOLFIRINOX or Gemcitabine/Abraxane) as confirmed by tumor
assessment within 21 days prior to registration.

- Patients with a prior malignancy and treated with curative intention are eligible if
all treatment of that malignancy was completed at least 2 years before registration
and the patient has no evidence of that disease at registration. Note: Less than 2
years is acceptable for malignancies with low risk of recurrence and/or no late
recurrence.

- Measurable disease per RECIST v1.1

- Patients must be willing to participate in the translational research part of the
trial and to undergo a tumor biopsy of the primary tumor and of the two metastatic
sites in the liver before trial treatment and after five cycles of nivolumab
treatment.

- Patients must be willing to travel to the hospital where IRE and biopsy will be
performed.

- Age = 18 years

- WHO performance status 0-1

- Life expectancy =4 months

- Adequate bone marrow function: neutrophil count = 1.0 x 109/L, platelet count = 100 x
109/L, hemoglobin = 80 g/L

- Adequate hepatic function: total bilirubin = 1.5 x ULN (except for patients with
Gilbert's disease = 3.0 x ULN), AST and ALT = 3 x ULN.

- Adequate renal function: estimated glomerular filtration rate (eGFR) = 50 mL/min/1.73
m2 (according to CKD-EPI formula).

- Adequate coagulation function: INR = 1.5 x ULN (the ULN for INR is defined with the
value 1.2 for all sites, in case no ULN is documented in the lab certificates/sheets).
In case patient is under anti-vitamin K treatment, INR >1.5 x ULN is allowed; however,
the patient has to be switched to LMWH treatment prior to any trial intervention.

- Women of childbearing potential must use effective contraception, are not pregnant or
lactating and agree not to become pregnant during trial treatment and until 5 months
after the last dose of nivolumab. A negative pregnancy test before inclusion into the
trial is required for all women of childbearing potential (for nivolumab product
information).

- Men agree not to donate sperm or to father a child during trial treatment and until 7
months after the last dose of nivolumab (for nivolumab product information).

Exclusion criteria:

- Clinically significant ascites that is not controllable.

- Prior surgery or radiotherapy to any PDAC disease site.

- Prior treatment with any immune checkpoint inhibitor.

- Concomitant or recent (within 100 days of registration) treatment with any other
experimental drug (enrollment in another clinical trial).

- Concomitant use of other anti-cancer drugs or radiotherapy.

- Severe or uncontrolled concurrent illness, such as cardiovascular disease (congestive
heart failure NYHA III or IV; unstable angina pectoris, history of myocardial
infarction within the last six months, serious arrhythmias requiring medication (with
exception of atrial fibrillation or paroxysmal supraventricular tachycardia),
significant QT-prolongation, uncontrolled hypertension.

- Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or
Hepatitis B Virus infection or any uncontrolled active systemic infection requiring
intravenous (i.v.) antimicrobial treatment.

- Known history of tuberculosis, known history of primary immunodeficiency, known
history of allogeneic organ transplant, receipt of live attenuated vaccine within 30
days prior to registration.

- Concomitant or prior use of immunosuppressive medication within 30 days of
registration, with the exceptions of intranasal and inhaled corticosteroids, or
systemic corticosteroids which must not exceed 10 mg/day of prednisone (or a dose
equivalent corticosteroid), and the premedication for chemotherapy

- Concomitant need for full anticoagulation treatment that cannot be stopped or bridged
for the performance of the biopsy/IRE procedures Note: Aspirin or other
acetylsalicylic acid containing drugs (up to 300 mg/day) are allowed

- Any concomitant drugs contraindicated for use with the trial treatment according to
the approved product information

- Known hypersensitivity to nivolumab or to any component of nivolumab, to stainless
steel or to contrast agents.

- Any other serious underlying medical (in particular coagulation deficiencies),
psychiatric, psychological, familial or geographical condition, which in the judgment
of the investigator may interfere with the planned staging, treatment and follow-up,
affect patient compliance or place the patient at high risk from treatment-related
complications.

Altri dati sulla sperimentazione nel registro primario dell’OMS

https://clinicaltrials.gov/show/NCT04212026

Altri dati sulla sperimentazione dalla banca dati dell’OMS (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT04212026

Altre informazioni sulla sperimentazione

Data di registrazione della sperimentazione

19.12.2019

Inserimento del primo partecipante

28.06.2020

Stato di reclutamento

Recruiting

Titolo scientifico (Fonte di dati: WHO)

Irreversible Electroporation (IRE) Followed by Nivolumab in Patients With Metastatic Pancreatic Cancer: a Multicenter Single-arm Phase II Trial

Tipo di sperimentazione (Fonte di dati: WHO)

Interventional

Disegno della sperimentazione (Fonte di dati: WHO)

Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Fase (Fonte di dati: WHO)

Phase 2

Punti finali primari (Fonte di dati: WHO)

The objective response rate (ORR) after the 5th dose of nivolumab of the reference liver metastasis that was not biopsied.

Punti finali secondari (Fonte di dati: WHO)

Objective Response Rate (ORR) after the 5th dose of nivolumab of the primary tumor site (pancreas).;ORR after the 5th dose of nivolumab of the IRE-treated liver metastasis;ORR based on best overall response;Immune ORR (iORR) based on best overall immune response;Progression free survival (PFS);Immune PFS (iPFS);Overall survival (OS);Adverse events

Contatto per informazioni (Fonte di dati: WHO)

Please refer to primary and secondary sponsors

Risultati della sperimentazione (Fonte di dati: WHO)

Sintesi dei risultati

ancora nessuna informazione disponibile

Collegamento ai risultati nel registro primario

ancora nessuna informazione disponibile

Informazioni sulla disponibilità dei dati dei singoli partecipanti

ancora nessuna informazione disponibile

Siti di esecuzione della sperimentazione

Siti di esecuzione in Svizzera (Fonte di dati: BASEC)

Basilea, Berna, Losanna, Zurigo

Paesi di esecuzione (Fonte di dati: WHO)

Switzerland

Contatto per maggiori informazioni sulla sperimentazione

Dati della persona di contatto in Svizzera (Fonte di dati: BASEC)

SAKK, Dr. Charlotte Maddox
+41 31 389 91 91
trials@sakk.ch

Contatto per informazioni generali (Fonte di dati: WHO)

Mathias Worni, MD;Daniela Bärtschi
Clarunis - St. Clara Hospital and University Hospital Basel
+41 31 389 91 91
trials@sakk.ch

Contatto per informazioni scientifiche (Fonte di dati: WHO)

Mathias Worni, MD;Daniela Bärtschi
Clarunis - St. Clara Hospital and University Hospital Basel
+41 31 389 91 91
trials@sakk.ch

Responsabile della sperimentazione

Sponsor principale (Fonte di dati: WHO)

Swiss Group for Clinical Cancer Research

Autorizzazione da parte della commissione d’etica (Fonte di dati: BASEC)

Nome della commissione d’etica che rilascia l’autorizzazione (nel caso di studi multicentrici solo la commissione direttiva)

Ethikkommission Nordwest- und Zentralschweiz EKNZ

Data di autorizzazione da parte della commissione d’etica

19.02.2020

Altri numeri di identificazione delle sperimentazioni

Numero di identificazione della sperimentazione della commissione d’etica (BASEC-ID) (Fonte di dati: BASEC)

2019-02408

Secondary ID (Fonte di dati: WHO)

SAKK 44/19