A Phase 1/2 Study of the Oral TRK Inhibitor LOXO-101 in Pediatric Patients With Advanced Solid or Primary Central Nervous System Tumors- SCOUT

Studio Clinico

Patologia: Altre neoplasie

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: No

Fase di studio: 1, II

Linee di trattamento: Prima linea, Seconda linea, Terza/N linea

Criteri di inclusione: 

Phase 1 (Closed):

- Dose escalation: Birth through 21 years of age at C1D1 with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and for which no standard or available systemic curative therapy exists; OR Infants from birth and older with a diagnosis of malignancy and with a documented NTRK fusion that has progressed or was nonresponsive to available therapies, and for which no standard or available curative therapy exists; OR Patients with locally advanced infantile fibrosarcoma who would require, in the opinion of the investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection. Phase I dose escalation cohorts are closed to enrollment.
- Dose expansion: In addition to the above stated inclusion criteria, patients must have a malignancy with a documented NTRK gene fusion with the exception of patients with infantile fibrosarcoma, congenital mesoblastic nephroma or secretory breast cancer. Patients with infantile fibrosarcoma, congenital mesoblastic nephroma or secretory breast cancer may enroll into this cohort with documentation of an ETV6 rearrangement by FISH or RT-PCR or a documented NTRK fusion by next generation sequencing.

Phase 2:

- Infants from birth and older at C1D1 with a locally advanced or metastatic infantile fibrosarcoma, patients with locally advanced infantile fibrosarcoma who would require, in the opinion of the investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection; OR Birth through 21 years of age at C1D1 with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and for which no standard or available systemic curative therapy exists with a documented NTRK gene fusion (or in the case of infantile fibrosarcoma, congenital mesoblastic nephroma or secretory breast cancer with documented ETV6 rearrangement (or NTRK3 rearrangement after discussion with the sponsor) by FISH or RT-PCR or a documented NTRK fusion by next generation sequencing) (identified through molecular assays as routinely performed at CLIA or other similarly certified laboratories). Patients with NTRK-fusion positive benign tumors are also eligible; OR Potential patients older than 21 years of age with a tumor diagnosis with histology typical of a pediatric patient and an NTRK fusion may be considered for enrollment following discussion between the local site Investigator and the Sponsor.
- Patients with primary CNS tumors or cerebral metastasis
- Karnofsky (those 16 years and older) or Lansky (those younger than 16 years) performance score of at least 50.
- Adequate hematologic function
- Adequate hepatic and renal function

Criteri di esclusione: 

- Major surgery within 14 days (2 weeks) prior to C1D1
- Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to C1D1, ongoing cardiomyopathy; current prolonged QTc interval > 480 milliseconds
- Active uncontrolled systemic bacterial, viral, or fungal infection
- Current treatment with a strong CYP3A4 inhibitor or inducer. Enzyme-inducing anti-epileptic drugs (EIAEDs) and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed.
Phase 2 only:
    - Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting TRK, including entrectinib, crizotinib and lestaurtanib. Patients who received a TRK inhibitor for less than 28 days of treatment and discontinued because of intolerance remain eligible.

Trattamento sperimentale: 

Larotrectinib (Vitravki, BAY2757556)

Trattamento di controllo: 

NA

Obiettivi primari dello studio: 

Phase 1: Number of participants with adverse events [ Time Frame: Up to 5 years ]
Phase 1: Severity of adverse events [ Time Frame: Up to 5 years ]
Phase 2: Overall response rate (ORR) by IRRC [ Time Frame: Up to 5 years ]
Proportion of subjects with confirmed best overall response of complete response or partial response, assessed by an independent radiology review committee (IRRC) using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or Response Assessment in Neuro-Oncology (RANO) as appropriate.

Centri partecipanti

Nord Italia

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2016-003498-16

Data di inserimento: 21.04.2021

Promotore

Bayer

CRO

/

Principal Investigator ITALIA

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Riferimento: Dr.ssa Michela Casanova

Telefono: 0223902588

Email: michela.casanova@istitutotumori.mi.it

Localita: Milano