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SNCTP000001942 | NCT02756845 | BASEC2015-00151

Multizentrische, offene Dosisreduktionsstudie der Phase 1 zur Beurteilung der Sicherheit und Wirksamkeit von Talimogen Laherparepvec bei pädiatrischen Patienten (0-21 Jahre) mit fortgeschrittenen nicht zentralnervösen Tumoren, die der direkten Injektionsbehandlung zugänglich sind

Base di dati: BASEC (Importata da 27.01.2022), WHO (Importata da 18.01.2022)
Cambiato: 18.01.2022
Categoria di malattie: Altro cancro

Descrizione riassuntiva della sperimentazione (Fonte di dati: BASEC)

Es handelt sich um eine multizentrische, offene Phase-1-Studie zu Talimogen Laherparepvec an pädiatrischen Patienten (0-21 Jahre) mit fortgeschrittenen Nicht-ZNS-Tumoren, die einer direkten Injektion im klinischen Rahmen zugänglich sind.
Talimogen Laherparepvec wird ca. 18 bis 27 pädiatrischen Patienten (0-21 Jahre) verabreicht.
Die Patienten werden, stratifiziert nach Alter und Herpes-simplex-Virustyp-1-Serostatus, in Kohorten eingeschlossen (3 bis 6 Patienten/Kohorte). Die DLTs werden auf Basis von 3 bis 6 bezüglich DLT auswertbaren Patienten ausgewertet.
Zunächst sollen 3 bis 6 HSV 1-seropositive Patienten im Alter zwischen 12 und < 21 Jahren eingeschlossen und mit 100 % der empfohlenen Dosis für Erwachsene behandelt werden (Kohorte A1). Als Anfangsdosis werden bis zu 4,0 ml mit 106 plaquebildenden Einheiten (PFU)/ml verabreicht, gefolgt von einer Dosis von bis zu 4,0 ml mit 108 PFU/ml 21 Tage (+ 3 Tage) später. Die nachfolgenden Dosen von bis zu 4,0 ml mit 108 PFU/ml werden anschliessend etwa alle 14 Tage (± 3 Tage) verabreicht. Die DLT-Beurteilungsphase umfasst 35 Tage ab der Erstverabreichung von Talimogen Laherparepvec. Wenn bei Kohorte A1 nach den DLT-Regeln keine Sicherheitsbedenken festgestellt werden, werden gemäss Studiendesign und Behandlungsschema weitere Kohorten eröffnet.
Sollte bei einer bestimmten Altersgruppe eine Dosisreduktion erforderlich sein, können weitere Teilnehmer rekrutiert und mit Talimogen Laherparepvec in niedrigerer Dosierung behandelt werden. Die Bezeichnung der Dosisreduktionskohorten erfolgt nach derselben Konvention auf Basis des Alters und des HSV 1-Serostatus bei Baseline (D1, D2, E1, E2, F1, F2).

Malattie studiate (Fonte di dati: BASEC)

Fortgeschrittene nicht zentralnervösen (Nicht-ZNS-)Tumoren, die einer direkten Injektion zugänglich sind.

Health conditions (Fonte di dati: WHO)

Advanced Non CNS Tumors

Malattia rara (Fonte di dati: BASEC)

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

Talimogen Laherparepvec wird mittels intralesionaler Injektion ausschließlich in injizierbare kutane, subkutane und nicht-viszerale Tumore sowie Tumore in Lymphknoten mit und ohne Ultraschallführung verabreicht.

Die an Tag 1 verabreichte erste Dosis Talimogen Laherparepvec beträgt maximal 4,0 ml der Konzentration 106 PFU/ml. Die zweite Injektion, maximal 4,0 ml der Konzentration 108 PFU/ml (oder bis zu 4,0 ml der Konzentration 106 PFU/ml in einer Dosisreduktionskohorte), wird 21 Tage (+ 3 Tage) nach der Erstinjektion verabreicht. Die nachfolgenden Dosen von jeweils bis zu 4,0 ml der Konzentration 108 PFU/ml (oder bis zu 4,0 ml der Konzentration 106 PFU/ml in einer Dosisreduktionskohorte) werden in Abständen von 14 Tagen (± 3 Tage) verabreicht. Das Intervall zwischen den Behandlungszyklen kann bei Toxizität auch verlängert werden.

Interventions (Fonte di dati: WHO)

Drug: Talimogene Laherparepvec

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

• 0 bis < 21 Jahre alt (zum Zeitpunkt der Einwilligung)
• Lokaler HSV 1-Serostatus mit messbarer bzw. nicht nachweisbarer Erkrankung
• Histologisch oder zytologisch bestätigter solider Nicht ZNS-Tumor, der nach
einer Standardbehandlung erneut aufgetreten ist (oder für
den keine Standardbehandlung verfügbar ist)
• Die Teilnehmer müssen für eine intraläsionale Behandlung in Frage kommen.
• Karnofsky-Leistungsindex von ≥ 70 % (Teilnehmer zwischen 12 und < 21 Jahren) bzw. ein Lansky-Index von ≤ 70 % (Kinder zwischen 2 und < 12 Jahren)
• Lebenserwartung von > 4 Monaten (ab Einschlussdatum)
• Ausreichende Organfunktion
• Gebärfähige Teilnehmerinnen: negativer Schwangerschaftstest

Criteri di esclusione (Fonte di dati: BASEC)

• Vorliegen von Leukämie, Non-Hodgkin-Lymphom, Hodgkin-Lymphom oder eines anderen hämatologischen Malignoms
• Knochenmarkbestrahlung in den letzten 6 Wochen vor Studieneinschluss bzw. in den letzten 3 Monaten vor Studieneinschluss, wenn bereits eine frühere kraniospinale Bestrahlung oder eine Bestrahlung von mindestens 60 % des Beckens durchgeführt wurde, oder in den letzten 2 Wochen vor Studieneinschluss, sofern eine lokale palliative Strahlentherapie durchgeführt wurde
• ZNS-Tumor oder klinisch aktive Hirnmetastasen
• Primär okuläres oder mukosales Melanom
• Anamnestische oder aktuelle Hinweise auf kongenitale melanozytäre Riesennävi, dysplastisches Nävus-Syndrom oder Xeroderma pigmentosum
• Sonstige anamnestisch bekannte Malignome in den zurückliegenden 5 Jahren
• Erster (oder Ursprünglicher) Immundefekt-Status wie zum Beispiel schwere kombinierte Immundefekt-Erkrankung

Inclusion/Exclusion Criteria (Fonte di dati: WHO)


Inclusion Criteria

- Subject's legally acceptable representative has provided informed consent/assent when
the subject is legally too young to provide informed consent/assent and the subject
has provided written assent based on local regulations and/or guidelines prior to any
study-specific activities/procedures being initiated.

- Should be willing to submit local HSV-1 serostatus within 28 days prior to enrollment.

- Subject must be a candidate for intralesional injection, defined as one or more of the
following:

- at least 1 injectable lesion = 10 mm in longest diameter

- multiple injectable lesions that in aggregate have a longest diameter of = 10 mm

- Life expectancy > 4 months from the date of enrollment.

- Male or female subjects 2 to = 21 years of age at the time of informed consent/assent.

- Histologically or cytologically confirmed non-CNS solid tumor that recurred after
standard/frontline therapy, or for which there is no standard/frontline therapy
available.

- Presence of measurable or non-measurable lesions as defined by irRC-RECIST

- Performance status as per protocol

- Female subject of childbearing potential should have a negative urine or serum
pregnancy test within 72 hours prior to dosing.

- Adequate organ function as defined in protocol

•Exclusion Criteria

- Diagnosis of leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, or other hematologic
malignancy.

- Radiotherapy to the bone marrow within 6 weeks prior to enrollment OR within 3 months
prior to enrollment if prior radiotherapy to the craniospinal axis or to at least 60%
of the pelvis was received; within 2 weeks prior to enrollment if local palliative
radiotherapy was received.

- Primary ocular or mucosal melanoma.

- History of other malignancy within the past 5 years with the following exception:

• malignancy treated with curative intent and with no known active disease present and
has not received chemotherapy for > 5 years before enrolment and felt to be at low
risk for recurrence by the treating physician.

- History or evidence of active autoimmune disease that requires systemic treatment (ie,
with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement
therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of
systemic treatment.

- Active herpetic skin lesions or prior complications of herpetic infection (eg,
herpetic keratitis or encephalitis).

- Prior treatment with talimogene laherparepvec or any other oncolytic virus.

- Prior treatment with a tumor vaccine.

- Requires intermittent or chronic treatment with an antiherpetic drug (eg, acyclovir),
other than intermittent topical use.

- Expected to require other cancer therapy while on study with the exception of local
palliative radiation treatment.

- Has acute or chronic active hepatitis B virus or hepatitis C virus infection or
received treatment with nucleotide analogs such as those used in the treatment of
hepatitis B virus (eg, lamivudine, adefovir, tenofovir, telbivudine, and entecavir),
ribavirin, or interferon alpha within 12 weeks of initiation of study treatment.

- Known or suspected human immunodeficiency virus (HIV) infection.

- Received live vaccine within 28 days prior to enrollment.

- No antiplatelet or anticoagulation medications allowed within 7 days prior
totalimogene laherparepvec injection except low-dose heparin needed to maintain venous
catheter patency.

- Female subject is pregnant or breast-feeding, or planning to become pregnant during
study treatment and through 3 months after the last dose of talimogene laherparepvec.

- Female subject of childbearing potential who is unwilling to use acceptable method(s)
of effective contraception during study treatment and through 3 months after the last
dose of talimogene laherparepvec. Note: Acceptable methods of effective contraception
are defined in the informed consent/assent form. Where required by local laws and
regulations, additional country-specific contraception requirements may be outlined in
a country-specific protocol supplement at the end of the Appendix Section of protocol.

- Subject has known sensitivity to any of the products or components to be administered
during dosing.

- Subject likely to not be available to complete all protocol-required study visits or
procedures, and/or to comply with all required study procedures to the best of the
subject and investigator's knowledge.

- History or evidence of any psychiatric disorder, substance abuse or any other
clinically significant disorder, condition or disease (with the exception of those
outlined above) that, in the opinion of the investigator or Amgen physician, if
consulted, would pose a risk to subject safety or interfere with the study evaluation,
procedures or completion.

- Subject who is unwilling to minimize exposure with his/her blood or other body fluids
to individuals who are at higher risks for HSV-1 induced complications
(immunosuppressed individuals, HIV-positive individuals, pregnant women, or children
under the age of 1 year) during talimogene laherparepvec treatment and through 28 days
after the last dose of talimogene laherparepvec.

- Evidence of clinically significant immunosuppression such as the following:

- primary immunodeficiency state such as severe combined immunodeficiency disease

- concurrent opportunistic infection

- receiving systemic immunosuppressive therapy (> 2 weeks prior to enrollment),
including oral steroid doses (with the exception of maintenance physiologic
replacement). Subjects who require intermittent use of steroids for inhalation or
local steroid injection will not be excluded from the study

- less than 6 months from autologous bone marrow transplant or stem cell infusion

- history of allogeneic bone marrow transplant

- History or evidence of xeroderma pigmentosum.

- Sexually active subjects and their partners unwilling to use a male or female latex
condom to avoid potential viral transmission during sexual contact while on treatment
and within 30 days after treatment with talimogene laherparepvec. For those with latex
allergies, polyurethane condoms may be used.

- Prior chemotherapy, treatment dose radiothera

Altri dati sulla sperimentazione nel registro primario dell’OMS

https://clinicaltrials.gov/show/NCT02756845

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

https://trialsearch.who.int/Trial2.aspx?TrialID=NCT02756845

Altre informazioni sulla sperimentazione

Data di registrazione della sperimentazione

15.12.2015

Inserimento del primo partecipante

16.08.2017

Stato di reclutamento

Recruiting

Titolo scientifico (Fonte di dati: WHO)

A Phase 1, Multi-center, Open-label, Dose De-escalation Study to Evaluate the Safety and Efficacy of Talimogene Laherparepvec in Pediatric Subjects With Advanced Non Central Nervous System Tumors That Are Amenable to Direct Injection

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 1

Punti finali primari (Fonte di dati: WHO)

Subject incidence of DLT

Punti finali secondari (Fonte di dati: WHO)

Subject incidence of adverse events.;Subject incidence of laboratory abnormalities;Overall Response Rate (ORR);Duration of Response (DOR);Time to Response (TTR);Time to Progression (TTP);Progression-free Survival (PFS);Overall Survival (OS)

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, Zurigo

Paesi di esecuzione (Fonte di dati: WHO)

Belgium, Canada, France, Italy, Spain, Switzerland, United States

Contatto per maggiori informazioni sulla sperimentazione

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

Christian Merkle
+41 41 369 0185
cmerkle@amgen.com

Contatto per informazioni generali (Fonte di dati: WHO)

MD;Amgen Call Center
Amgen
866-572-6436
medinfo@amgen.com

Contatto per informazioni scientifiche (Fonte di dati: WHO)

MD;Amgen Call Center
Amgen
866-572-6436
medinfo@amgen.com

Responsabile della sperimentazione

Sponsor principale (Fonte di dati: WHO)

Amgen

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)

Kantonale Ethikkommission Zürich

Data di autorizzazione da parte della commissione d’etica

01.02.2016

Altri numeri di identificazione delle sperimentazioni

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

2015-00151

Secondary ID (Fonte di dati: WHO)

2015-003645-25
20110261