Torna alla panoramica
SNCTP000002813 | NCT03157128 | BASEC2017-02259

Eine Studie der Phase 1/2 zu oral verabreichtem Selpercatinib (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 28.03.2024), WHO (Importata da 20.03.2024)
Cambiato: 13 mar 2024, 01:00
Categoria di malattie: Altro cancro

Descrizione riassuntiva della sperimentazione (Fonte di dati: BASEC)

Die Studie wird voraussichtlich mehrere Jahre dauern. Sie wird in zwei Phasen durchgeführt: Dosiseskalation und Dosisexpansion. Die Dosiseskalation ist abgeschlossen. In der Schweiz, wird jedoch nur die Dosisexpansion durchgeführt. Auf der Grundlage der Krebsart und vorhergehenden Krebstherapien werden Patienten in eine von sieben Gruppen aufgenommen (sogenannte Expansionskohorten). Bis zu 1070 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 zu Beginn der Studie 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

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 2 Wochen vor dem geplanten Beginn von Selpercatinib.

Inclusion/Exclusion Criteria (Fonte di dati: WHO)

Gender: All
Maximum age: N/A
Minimum age: 12 Years

Key Inclusion Criteria:

For Phase 1:

- Participants with a locally advanced or metastatic solid tumor that:

- Has progressed on or is intolerant to standard therapy, or

- For which 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 multikinase inhibitors (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) greater than or equal to (=) 40 percent (%) (age less than [<] 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: Participants 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 participants with evidence of a RET gene
alteration in tumor

- 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:

- Cohorts 1-4 without measurable disease

- MCT not meeting the requirements for Cohorts 3 or 4

- 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: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who
discontinued another RET inhibitor may be eligible with prior Sponsor approval

- Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET
fusion; determined to be medically operable and tumor deemed resectable by a thoracic
surgical oncologist, without prior systemic treatment for NSCLC

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: Participants
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 2 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 participants 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 Common Terminology Criteria
for Adverse Events (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. Participants 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) greater than (>) 470 milliseconds
(msec)

- Participants with implanted pacemakers may enter the study without meeting QTc
criteria due to nonevaluable measurement if it is possible to monitor for QT
changes.

- Participants with bundle branch block may be considered for study entry if QTc is
appropriate by a formula other than Fridericia's and if it is possible to monitor
for QT changes.

- Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or
inducers and certain prohibited concomitant medications

- Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior
systemic therapy for NSCLC.

Altri dati sulla sperimentazione nel registro primario dell’OMS

https://clinicaltrials.gov/ct2/show/NCT03157128

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

https://trialsearch.who.int/Trial2.aspx?TrialID=NCT03157128
Altre informazioni sulla sperimentazione

Stato di reclutamento

Recruiting

Titolo scientifico (Fonte di dati: WHO)

A Phase 1/2 Study of Oral Selpercatinib (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 1: MTD;Phase 1: RP2D;Phase 2: Objective Response Rate

Punti finali secondari (Fonte di dati: WHO)

Phase 1: Number of Participants with a Treatment-Related Adverse Event(s) (TRAE[s]);Phase 1: Number of Participants with an Abnormal Laboratory or Physical Exam Result(s);Phase 1: Overall Response Rate (ORR) based on RECIST 1.1 or RANO, as Appropriate to Tumor Type;Phase 2: ORR (by Investigator);Phase 2: Best Change in Tumor Size from Baseline (by IRC and Investigator);Phase 2: Duration of Response (DOR; by IRC and Investigator);Phase 2: Central Nervous System (CNS) ORR (by IRC);Phase 2: CNS DOR (by IRC);Phase 2: Time to Any and Best Response (by IRC and Investigator);Phase 2: CBR (by IRC and Investigator);Phase 2: PFS (by IRC and Investigator);Phase 2: Overall Survival (OS);Phase 2: Percentage of Participants with any Serious Adverse Event (SAE[s]);Phase 1 and 2: Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve of LOXO-292 (Selpercatinib);Phase 1 and 2: PK: Maximum Concentration (Cmax) of LOXO-292 (Selpercatinib)

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)

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST);There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
Eli Lilly and Company
1-317-615-4559
ClinicalTrials.gov@lilly.com

Contatto per informazioni scientifiche (Fonte di dati: WHO)

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST);There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
Eli Lilly and Company
1-317-615-4559
ClinicalTrials.gov@lilly.com

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)

J2G-OX-JZJA
LOXO-RET-17001
2017-000800-59
17477
Torna alla panoramica