A Multicenter, Randomized, Open-label, 3-Arm Phase 3 Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer

CompletadoFase 3ClinicalTrials.gov

ID: NCT02928224Tipo: INTERVENTIONALInicio: 13 de oct de 2016Fin estimado: 10 de nov de 2022

Traducción no disponible, mostrando original

Resumen

This is a multicenter, randomized, open-label, 3-arm Phase 3 study to evaluate encorafenib + cetuximab plus or minus binimetinib versus Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab, as controls, in patients with BRAFV600E mCRC whose disease has progressed after 1 or 2 prior regimens in the metastatic setting. The study contains a Safety Lead-in Phase in which the safety and tolerability of encorafenib + binimetinib + cetuximab will be assessed prior to the Phase 3 portion of the study.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Age ≥ 18 years at time of informed consent
Histologically- or cytologically-confirmed CRC that is metastatic
Presence of BRAFV600E in tumor tissue as previously determined by a local assay at any time prior to Screening or by the central laboratory
Progression of disease after 1 or 2 prior regimens in the metastatic setting
Evidence of measurable or evaluable non-measurable disease per RECIST, v1.1
Adequate bone marrow, cardiac, kidney and liver function
Able to take oral medications
Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy from screening through follow-up if of childbearing potential
Males must agree to take appropriate precautions to avoid fathering a child from screening through follow-up

Criterios de exclusión

Prior treatment with any RAF inhibitor, MEK inhibitor, cetuximab, panitumumab or other epidermal growth factor receptor (EGFR) inhibitors
Prior irinotecan hypersensitivity or toxicity that would suggest an inability to tolerate irinotecan 180 mg/m2 every 2 weeks
Symptomatic brain metastasis or leptomeningeal disease
History or current evidence of retinal vein occlusion or current risk factors for retinal vein occlusion (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
Known history of acute or chronic pancreatitis
History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to randomization
Uncontrolled blood pressure despite medical treatment
Impaired GI function or disease that may significantly alter the absorption of encorafenib or binimetinib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption)
Concurrent or previous other malignancy within 5 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy
History of thromboembolic or cerebrovascular events ≤ 6 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli
Concurrent neuromuscular disorder that is associated with the potential of elevated creatine (phosphor)kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
Residual common terminology criteria for adverse events (CTCAE) ≥ Grade 2 toxicity from any prior anticancer therapy, with the exception of Grade 2 alopecia or Grade 2 neuropathy
Known history of HIV infection
Active hepatitis B or hepatitis C infection
Known history of Gilbert's syndrome
Known contraindication to receive cetuximab or irinotecan at the planned doses

Intervenciones

drug

Encorafenib

Orally, once daily.

drug

Binimetinib

Orally, twice daily.

drug

Cetuximab

Standard of care.

drug

Irinotecan

Standard of care.

drug

Folinic Acid

Standard of care.

drug

5-Fluorouracil

Standard of care.

Ubicaciones

CLINICA PERGAMINO S.A. (Centro de Investigacion Pergamino S.A.)

Pergamino, Buenos Aires, Argentina

Centro Medico INFINITO

Santa Rosa, La Pampa Province, Argentina

Centro Medico CAIPO (Centro para la Atención del paciente Oncológico)

San Miguel de Tucumán, Tucumán Province, Argentina

Clinica Universitaria Reina Fabiola

Córdoba, Argentina

Centro Oncologico Riojano Integral - CORI

La Rioja, Argentina

Patrocinadores

PrincipalPfizer

ColaboradorMerck KGaA, Darmstadt, Germany

ColaboradorPierre Fabre Medicament

ColaboradorOno Pharmaceutical Co. Ltd

Aviso: La información de este ensayo proviene de fuentes públicas y tiene carácter exclusivamente informativo. No constituye asesoramiento médico, regulatorio ni de ningún otro tipo. Las traducciones son automatizadas y no poseen validez oficial. Consultá siempre con un profesional de la salud. Ver Términos de Uso.

A Multicenter, Randomized, Open-label, 3-Arm Phase 3 Stud... | EligiMed