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SNCTP000002813 | NCT03157128 | BASEC2017-02259

Eine Studie der Phase 1/2 zu oral verabreichtem LOXO-292 an Patienten mit fortgeschrittenen soliden Tumoren, einschliesslich RET-Fusion-positiver solider Tumoren, medullärem Schilddrüsenkarzinom und anderer Tumoren mit RET-Aktivierung (LIBRETTO-001)

Base di dati: BASEC (Importata da 25.09.2020), WHO (Importata da 20.09.2020)
Cambiato: 17.09.2020
Categoria di malattie: Altro cancro

Descrizione riassuntiva della sperimentazione (Fonte di dati: BASEC)

Die Studie wird voraussichtlich etwa 28 Monate dauern. Sie wird in zwei Phasen durchgeführt: Dosiseskalation und Dosisexpansion. Die Dosiseskalation läuft noch. In der Schweiz, wird jedoch nur die Dosisexpansion durchgeführt. Auf der Grundlage der Krebsart und vorhergehenden Krebstherapien werden Patienten in eine von fünf Gruppen aufgenommen (sogenannte Expansionskohorten).
Bis zu 870 Personen werden voraussichtlich an der klinischen Studie teilnehmen. In der Schweiz, werden nur Patienten im Alter von 18 Jahren oder älter in der Studie eingeschlossen. Die Studie wird an ungefähr 100 Prüfzentren in den USA, in Europa und Asien durchgeführt.
Die hier beschriebene Studie ist die erste Studie am Menschen zum Prüfmedikament LOXO-292. Prüfmedikament bedeutet, dass LOXO-292 derzeit von keiner Arzneimittel- oder Zulassungsbehörde zugelassen wurde.

Malattie studiate (Fonte di dati: BASEC)

Patienten mit fortgeschrittenen soliden Tumoren, einschließlich nicht-kleinzelligem Bronchialkarzinom (Non-Small Cell Lung Cancer, NSCLC) mit RET-Fusion, medullärem Schilddrüsenkarzinom und anderer Tumoren mit erhöhter RET-Aktivität.

Health conditions (Fonte di dati: WHO)

Non-Small Cell Lung Cancer;Medullary Thyroid Cancer;Colon Cancer;Any Solid Tumor

Malattia rara (Fonte di dati: BASEC)

No

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

LOXO-292 ist ein Tyrosinkinasehemmer, der entwickelt wurde, um ein Protein namens RET so stark wie möglich zu hemmen und andere Signalwege in der Krebszelle zu blockieren. Infolgedessen kann man davon ausgehen, dass LOXO-292 bei Tumoren mit Abweichungen im RET-Gen wirksamer sein könnte. Bei nicht-kleinzelligem Bronchialkarzinom und Schilddrüsenkarzinom treten Abweichungen im RET-Gen am häufigsten auf, aber sie können auch bei anderen Tumorarten vorkommen.

Interventions (Fonte di dati: WHO)

Drug: LOXO-292 (selpercatinib)

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

Einschlusskriterien Phase 1:
1. Patienten mit einem lokal fortgeschrittenen oder metastasierten soliden Tumor, die:
• Unter einer Standardtherapie fortgeschritten sind oder die eine Standardtherapie nicht vertragen oder
• Es ist keine Standardtherapie vorhanden oder
• Patienten, die eine Standardtherapie ablehnen oder
• Nach Einschätzung des Prüfarztes für eine Standardtherapie nicht infrage kommen oder diese wahrscheinlich nicht vertragen oder keinen signifikanten klinischen Nutzen daraus ziehen würden.
2. Eine beliebige Anzahl vorheriger MKIs mit Anti-RET-Aktivität ist erlaubt. Beispiele für Multi-Kinase-Inhibitoren (MKIs) mit Anti-RET-Aktivität siehe Appendix A.
3. Nachweis einer RET-Genalteration ist initial nicht gefragt.

Criteri di esclusione (Fonte di dati: BASEC)

Ausschlusskriterien für Phase 1 und Phase 2:
1. Phase 2, Kohorte 1-4, das Vorliegen eines zusätzlichen validierten, krebsinduzierenden, genetischen Faktors, der eine Resistenz gegen die Selpercatinib-Behandlung verursachen könnte.
2. Phase 2, Kohorte 1-5: vorherige Behandlung mit einem selektiven RET-Inhibitor(en)
3. Behandlung mit einem Prüfpräparat oder einer Krebstherapie innerhalb von 5 Halbwertszeiten oder 2 Wochen (maßgeblich ist der kürzere Zeitraum) vor dem geplanten Beginn von Selpercatinib.
4. Größere Operation (mit Ausnahme des Legens eines vaskulären Zugangs) innerhalb von 4 Wochen vor dem geplanten Beginn von Selpercatinib.

Inclusion/Exclusion Criteria (Fonte di dati: WHO)


Key Inclusion Criteria:

For Phase 1

- Patients with a locally advanced or metastatic solid tumor who:

- have progressed on or are intolerant to standard therapy, or

- no standard therapy exists, or in the opinion of the Investigator, are not
candidates for or would be unlikely to tolerate or derive significant clinical
benefit from standard therapy, or

- decline standard therapy

- Prior MKIs with anti-RET activity are allowed.

- A RET gene alteration is not required initially. Once adequate PK exposure is
achieved, evidence of RET gene alteration in tumor and/or blood is required as
identified through molecular assays, as performed for clinical evaluation.

- Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as
appropriate to tumor type.

- Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance
Score (LPS) = 40% (age < 16 years) with no sudden deterioration 2 weeks prior to the
first dose of study treatment.

- Adequate hematologic, hepatic and renal function.

- Life expectancy of at least 3 months.

For Phase 2

As for phase 1 with the following modifications:

- For Cohort 1 (up to 250 patients): Subjects must have received prior standard therapy
appropriate for their tumor type and stage of disease, or in the opinion of the
Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate
standard of care therapy.

- Cohorts 1 and 2: enrollment will be restricted to patients with evidence of a RET gene
alteration in tumor.

- Cohorts 1 and 2: at least one measurable lesion as defined by RECIST 1.1 or RANO, as
appropriate to tumor type and not previously irradiated.

- Cohorts 3 and 4: Enrollment closed.

- Cohort 5: (up to 200 patients):

- Cohorts 1 and 2 without measurable disease;

- MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with
neuroendocrine features/differentiation, or poorly differentiated thyroid cancers
with other RET alteration/activation may be allowed with prior Sponsor approval;

- cfDNA positive for a RET gene alteration not known to be present in a tumor
sample.

- Cohort 6 (up to 50 patients):

- Patients who otherwise are eligible for Cohorts 1, 2 or 5 who discontinued
another RET inhibitor due to intolerance may be eligible with prior Sponsor
approval.

Key Exclusion Criteria (Phase 1 and Phase 2):

- Phase 2 Cohorts 1 and 2: an additional known oncogenic driver.

- Cohorts 3 and 4: Enrollment closed.

- Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor

Notes:

Patients otherwise eligible for Cohorts 1, 2, and 5 who discontinued another selective RET
inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval.

- Investigational agent or anticancer therapy (including chemotherapy, biologic therapy,
immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5
half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292
(selpercatinib). In addition, no concurrent investigational anti-cancer therapy is
permitted.

Note:

Potential exception for this exclusion criterion will require a valid scientific
justification and approval from the Sponsor.

- Major surgery (excluding placement of vascular access) within 4 weeks prior to planned
start of LOXO-292 (selpercatinib).

- Radiotherapy with a limited field of radiation for palliation within 1 week of planned
start of LOXO-292 (selpercatinib), with the exception of patients receiving radiation
to more than 30% of the bone marrow or with a wide field of radiation, which must be
completed at least 4 weeks prior to the first dose of study treatment.

- Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of
starting study treatment with the exception of alopecia and Grade 2, prior
platinum-therapy related neuropathy.

- Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated
spinal cord compression. Patients are eligible if neurological symptoms and CNS
imaging are stable and steroid dose is stable for 14 days prior to the first dose of
LOXO-292 (selpercatinib) and no CNS surgery or radiation has been performed for 28
days, 14 days if stereotactic radiosurgery [SRS].

- Clinically significant active cardiovascular disease or history of myocardial
infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or
prolongation of the QT interval corrected (QTcF) > 470 msec.

- Required treatment with certain strong CYP3A4 inhibitors or inducers and certain
prohibited concomitant medications.

Altri dati sulla sperimentazione nel registro primario dell’OMS

https://clinicaltrials.gov/show/NCT03157128

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

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT03157128

Altre informazioni sulla sperimentazione

Data di registrazione della sperimentazione

09.05.2017

Inserimento del primo partecipante

09.05.2017

Stato di reclutamento

Recruiting

Titolo scientifico (Fonte di dati: WHO)

A Phase 1/2 Study of Oral LOXO-292 in Patients With Advanced Solid Tumors, Including RET Fusion-Positive Solid Tumors, Medullary Thyroid Cancer, and Other Tumors With RET Activation (LIBRETTO-001)

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/Phase 2

Punti finali primari (Fonte di dati: WHO)

Phase 2: Objective Response Rate;Phase 1: Recommended Phase 2 dose (RP2D);Phase 1: Maximum tolerated dose (MTD)

Punti finali secondari (Fonte di dati: WHO)

Phase 2: Plasma concentrations of LOXO-292 (selpercatinib) and PK parameters, including but not limited to AUC0-24, Cmax, and Tmax.;Phase 2: Frequency, severity and relatedness of TEAEs and SAEs, changes in hematology and blood chemistry values, assessments of physical examinations, vital signs and ECGs.;Phase 2: OS;Phase 2: PFS (by IRC and Investigator);Phase 2: CBR (by IRC and Investigator);Phase 2: time to any and best response (by IRC and Investigator);Phase 2: CNS DOR (by IRC);Phase 2: CNS ORR (by IRC);Phase 2: DOR (by IRC and Investigator);Phase 2: best change in tumor size from baseline (by IRC and Investigator);Phase 2: ORR (by Investigator);Phase 1: ORR based on RECIST 1.1 or RANO, as appropriate to tumor type.;Phase 1: Plasma concn of LOXO-292 (selpercatinib) and PK parameters, including but not limited to area under the curve from time 0 to 24 hrs (AUC0-24), max drug concn (Cmax), time to max plasma concn (Tmax), and degree of accumulation;Phase 1: Frequency, severity, and relatedness of TEAEs and serious adverse events (SAEs), changes in hematology and blood chemistry values, assessments of physical examinations, vital signs, and electrocardiograms (ECGs).

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)

Luzern

Paesi di esecuzione (Fonte di dati: WHO)

Australia, Canada, Denmark, France, Germany, Hong Kong, Israel, Italy, Japan, Korea, Republic of, Singapore, Spain, Switzerland, Taiwan, United Kingdom, United States

Contatto per maggiori informazioni sulla sperimentazione

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

Prof. Dr. med. Oliver Gautschi
+41 41 205 58 60
oliver.gautschi@luks.ch

Contatto per informazioni generali (Fonte di dati: WHO)

Liz Olek, DO, MPH;Patient Advocacy
Loxo Oncology
855-RET-4-292 (855-738-4292)
clinicaltrials@loxooncology.com

Contatto per informazioni scientifiche (Fonte di dati: WHO)

Liz Olek, DO, MPH;Patient Advocacy
Loxo Oncology
855-RET-4-292 (855-738-4292)
clinicaltrials@loxooncology.com

Responsabile della sperimentazione

Sponsor principale (Fonte di dati: WHO)

Loxo Oncology, Inc.

Altri sponsor (Fonte di dati: WHO)

Eli Lilly and Company

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

28.03.2018

Altri numeri di identificazione delle sperimentazioni

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

2017-02259

Secondary ID (Fonte di dati: WHO)

2017-000800-59
LOXO-RET-17001 /J2G-OX-JZJA