Resumen

Este es un estudio abierto, internacional, multicéntrico, de fase 3 de CGT9486 en combinación con sunitinib. Es un estudio en múltiples partes que incluirá aproximadamente 442 pacientes. La Parte 1 consiste en dos evaluaciones: 1) confirmar la dosis de una formulación actualizada de CGT9486 para su uso en partes posteriores en aproximadamente 20 pacientes que hayan recibido al menos una línea de tratamiento previa para GIST, y 2) evaluar el potencial de interacciones fármaco-fármaco entre CGT9486 y sunitinib en aproximadamente 18 pacientes que hayan recibido al menos dos inhibidores de tirosina quinasa (TKI) previos para GIST. La segunda parte del estudio incluirá aproximadamente 388 pacientes intolerantes al tratamiento previo con imatinib o que hayan fracasado con este, y comparará la eficacia de CGT9486 más sunitinib frente a sunitinib en monoterapia, con aleatorización de los pacientes en proporción 1:1. Además, un subestudio de interacciones fármaco-fármaco investigará el potencial de CGT9486 como inductor de CYP3A4 en aproximadamente 16 pacientes que hayan recibido al menos una línea de tratamiento previa para GIST.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Histologically confirmed locally advanced, metastatic, and/or unresectable GIST. Molecular pathology report must be available for Part 2; if molecular pathology report is unavailable or inadequate, an archival or fresh tumor tissue sample will be required to evaluate mutational status prior to randomization.
Documented disease progression on or intolerance to imatinib
Subjects must have received the following treatment:
DDI Substudy/Part 1a: Treatment with ≥1 prior lines of therapy for GIST Part 1b: Treatment with ≥2 prior TKI for GISTs Part 2: Prior treatment with imatinib only
Have at least 1 measurable lesion according to mRECIST v1.1 (Part1a, Part 1b, Part 2)
ECOG - 0 to 2
Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits

Criterios de exclusión

Known PDGFR driving mutations or known succinate dehydrogenase deficiency
Clinically significant cardiac disease
Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug
Gastrointestinal abnormalities including, but not limited to, significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption
Any active bleeding excluding hemorrhoidal or gum bleeding
Seropositive for HIV 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody.
Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening
Received strong CYP3A4 inhibitors or inducers
Received sunitinib within 3 weeks (Part 1a, Part 1b, DDI Substudy)

Intervenciones

drug

CGT9486 plus sunitinib

Participants will receive both CGT9486 and sunitinib orally until study stopping rules are met.

drug

CGT9486

Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.

drug

Sunitinib

Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.

drug

Sunitinib

Participants will receive sunitinib orally until study stopping rules are met.

drug

Midazolam

Participants will receive a single-dose of midazolam on Day 1 and Day 16

drug

CGT9486 plus sunitinib

Patients will receive CGT9486 orally starting on Day 2 and sunitinib starting on Day 16 until study stopping rules are met.

Estudio clínico de fase 3, aleatorizado, abierto y multicéntrico de CGT9486 + sunitinib frente a sunitinib en sujetos con tumores del estroma gastrointestinal localmente avanzados, irresecables o metastásicos.

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

CGT9486 plus sunitinib

CGT9486

Sunitinib

Sunitinib

Midazolam

CGT9486 plus sunitinib

Ubicaciones

Instituto Alexander Fleming

Instituto Oncologico de Cordoba (IONC)

Patrocinadores