Resumen

Este estudio se realiza para determinar si tucatinib combinado con otros fármacos oncológicos funciona mejor que el tratamiento estándar en participantes con cáncer colorrectal HER2 positivo. El estudio también determinará qué efectos adversos se producen cuando los participantes toman esta combinación de fármacos. Un efecto adverso es cualquier efecto que un fármaco produce en el organismo además de tratar la enfermedad. Los participantes de este estudio tienen cáncer colorrectal que se ha diseminado por el organismo (metastásico) y/o que no puede ser extirpado con cirugía (irresecable). Los participantes serán asignados de forma aleatoria al grupo de tucatinib o al grupo de tratamiento estándar. El grupo de tucatinib recibirá tucatinib, trastuzumab y mFOLFOX6. El grupo de tratamiento estándar recibirá: * mFOLFOX6 solo, * mFOLFOX6 con bevacizumab, o * mFOLFOX6 con cetuximab. mFOLFOX6 es una combinación de múltiples fármacos. Todos los fármacos administrados en este estudio se utilizan para tratar este tipo de cáncer.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Histologically and/or cytologically confirmed adenocarcinoma of the colon or rectum which is locally advanced unresectable or metastatic
Able to provide the most recently available formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks (or freshly sectioned slides) obtained prior to treatment initiation to a central laboratory
If archival tissue is not available, a newly-obtained baseline biopsy of an accessible tumor lesion is required within 35 days prior to start of study treatment
HER2+ disease as determined by a tissue based assay performed at a central laboratory.
Participant has rat sarcoma viral oncogene homolog wild-type (RAS WT) disease as determined by local or central testing. For central RAS analysis, tissue sample must be analyzed within 1 year of biopsy date.
Radiographically measurable disease per RECIST v1.1 with:
At least one site of disease that is measurable and that has not been previously irradiated, or
If the participant has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
CNS Inclusion - based on contrast brain magnetic resonance imaging, participants may have any of the following:
No evidence of brain metastases
Previously treated brain metastases which are asymptomatic

Criterios de exclusión

Prior systemic anticancer therapy for colorectal cancer (CRC) in the locally advanced unresectable or metastatic setting; note that participants may have received a maximum of 2 doses of mFOLFOX6 in the locally advanced/unresectable or metastatic setting prior to randomization.
Note: May have received chemotherapy for CRC in the adjuvant setting if it was completed \>6 months prior to enrollment
Radiation therapy within 14 days prior to enrollment (or within 7 days in the setting of stereotactic radiosurgery)
Previous treatment with anti-HER2 therapy
Ongoing Grade 3 or higher neuropathy
Active or untreated gastrointestinal (GI) perforation at the time of screening.

Intervenciones

drug

tucatinib

300mg given by mouth (orally) twice daily

drug

trastuzumab

8mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 day 1, followed by 6mg/kg given by IV every 3 weeks thereafter.

drug

bevacizumab

5mg/kg given by IV every 2 weeks

drug

cetuximab

400mg/m2 loading dose will be given by IV on Cycle 1 day 1, followed by 250mg/m2 given by IV weekly

drug

oxaliplatin

85mg/m2 given by IV every 2 weeks. Component of mFOLFOX6.

drug

leucovorin

400mg/ m2 given by IV every 2 weeks. Component of mFOLFOX6.

drug

levoleucovorin

200mg/ m2 given by IV every 2 weeks. May be given in place of leucovorin. Component of mFOLFOX6.

drug

fluorouracil

400mg/m2 given by IV bolus then 2400mg/m2 given by continuous IV infusion (over 46-48 hours) every 2 weeks. Component of mFOLFOX6.

Ubicaciones

Centro de Investigacion Pergamino SA

Pergamino, Buenos Aires, Argentina

RECRUITING

Instituto Medico de la Fundacion Estudios Clinicos

Rosario, Santa Fe Province, Argentina

RECRUITING

Instituto Medico Especializado Alexander Fleming

Buenos Aires, Argentina

RECRUITING

Hospital Britanico de Buenos Aires

CABA, Argentina

RECRUITING

IONC Instituto Oncologico de Cordoba Fundacion Richardet Longo

Córdoba, Argentina

RECRUITING

CEMAIC - Centro Medico Privado

Córdoba, Argentina

RECRUITING

Estudio Abierto, Aleatorizado de Fase 3 de Tucatinib en Combinación con Trastuzumab y mFOLFOX6 Versus mFOLFOX6 con o sin Cetuximab o Bevacizumab como Tratamiento de Primera Línea en Sujetos con Cáncer Colorrectal Metastásico HER2+

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

tucatinib

trastuzumab

bevacizumab

cetuximab

oxaliplatin

leucovorin

levoleucovorin

fluorouracil

Ubicaciones

Centro de Investigacion Pergamino SA

Instituto Medico de la Fundacion Estudios Clinicos

Instituto Medico Especializado Alexander Fleming

Hospital Britanico de Buenos Aires

IONC Instituto Oncologico de Cordoba Fundacion Richardet Longo

CEMAIC - Centro Medico Privado

Patrocinadores

Contactos

Pfizer CT.gov Call Center