metastatic colorectal cancer
Conditions
Interventions
Treatment with LGX818 in combination with cetuximab with or without BYL719.
Cetuximab will be administered intravenously. Startingdose: 400mg/m2 followed
by 250 mg/m2 weekly
LGX818 will be supplied
Sponsors
Array Biopharma Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Histological or cytological proof of metastatic colorectal cancer (mCRC) 2. Progression after at least one prior standard of care regimen or be intolerant to irinotecan-based regimens 3. KRAS wild-type and BRAF V600E mutation, or any other BRAF V600 mutation 4. Phase II only: fresh tumor biopsy at baseline 5. Evidence of measurable disease, as determined by RECIST v1.1. 6. Life expectancy >= 3 months 7. ECOG performance status
Exclusion criteria
Exclusion criteria: 1. Phase II only: previous treatment with cetuximab, panitumumab, other EGFR inhibitors, RAF-inhibitors, PI3K-inhibitors, and/or MEK-inhibitors 2. Symptomatic or untreated leptomeningeal disease 3. Symptomatic brain metastasis. 4. Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs or with fasting glucose >=7.8 mmol/L, history of clinically significant gestational diabetes mellitus or documented steroid-induced diabetes mellitus 5. Known acute or chronic pancreatitis 6. Clinically significant cardiac disease including any of the following: Congestive heart failure requiring treatment (NYHA grade >= 2), LVEF 480 msec 7. Any of the following laboratory values at Screening/baseline: •Absolute neutrophil count (ANC) 1.5 x ULN or Creatinin Clearance 1.5 x ULN, except for patients with Gilbert*s syndrome, who may be included if total bilirubin is 2.5 x ULN, or > 5 x ULN if liver metastases are present 8. Impairment of gastrointestinal (GI) function or GI disease which may alter the absorption of LGX818 9. Previous or concurrent malignancy. Exceptions: adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix without evidence of recurrence for at least 3 years prior to study entry; or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry. 10. Pregnant or nursing (lactating) women 11. History of thromboembolic or cerebrovascular events within the last 6 months, including transient ischemic attack, deep vein thrombosis, or pulmonary embolism. 12. Radiation therapy (> 30% of the bone marrow reserve), chemotherapy, biological therapy (e.g., antibodies) within
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of DLTs, progression free survival | — |
Secondary
| Measure | Time frame |
|---|---|
| Incidence and severity of adverse events, pharmacokinetics, overall response rate, duration of response, time to response, progression free survival and overall survival. | — |
Countries
Netherlands
Outcome results
None listed