Clinical trial NCT02041481 (phase 1, status: completed)
Conditions: recurrent colon cancer, recurrent rectal cancer, stage iva colon cancer, stage iva rectal cancer, stage ivb colon cancer, stage ivb rectal cancer
ICD codes: C18.2, C18.4, C18.6, C18.7, C18.9, D12.2, D12.3, G47.13, J01.41, K11.22, K12.0, N96, F33.8, G03.2, C18.2, C18.4, C18.6, C18.7, C18.9, D12.2, D12.3, C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2, C18.2, C18.4, C18.6, C18.7, C18.9, D12.2, D12.3, C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2
Drugs: mek inhibitor mek162, leucovorin calcium, fluorouracil, oxaliplatin
SMILES: CN1C=NC2=C(F)C(NC3=CC=C(Br)C=C3F)=C(C=C12)C(=O)NOCCO, NC1=NC(=O)C2=C(NC[C@H](CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N2C=O)N1, [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1, [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Eligibility criteria:

        Inclusion Criteria:

          -  Patients with pathologically confirmed colon or rectal cancer who have received and
             progressed or failed following a fluoropyrimidine, irinotecan, and oxaliplatin based
             chemotherapy regimens will be eligible for this study; patients who have a known
             Kirsten rat sarcoma viral oncogene homolog (KRAS)/v-raf murine sarcoma viral oncogene
             homolog B (BRAF) wild type tumor should have progressed or failed following cetuximab
             or panitumumab based chemotherapy; prior bevacizumab or regorafenib exposure is not
             mandated on this study as some patients are deemed poor candidates for
             anti-angiogenesis therapy and never receive these agents

          -  Patients should have measurable disease defined as a minimum of one tumor measuring >=
             10 mm on computed tomography (CT) scans

          -  Signed written informed consent

          -  Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

          -  Hemoglobin (Hgb) >= 9 g/dL without transfusions

          -  Platelets (PLT) >= 100 x 10^9/L without transfusions

          -  Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 2.5 × upper
             limit of normal (ULN); patient with liver metastases =< 5 ×ULN

          -  Total bilirubin =< ULN

          -  Creatinine =< 1.5 mg/dL

          -  Left ventricular ejection fraction (LVEF) >= 50% as determined by a multigated
             acquisition (MUGA) scan or echocardiogram

          -  Corrected QT (QTc) interval =< 480 ms

          -  Able to take oral medications

          -  Patient is deemed by the investigator to have the initiative and means to be compliant
             with the protocol (treatment and follow-up)

          -  Negative serum beta-human chorionic gonadotropin (HCG) test (female patient of
             childbearing potential only) performed locally within 72 hrs prior to first dose

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 1

        Exclusion Criteria:

          -  History or current evidence of retinal vein occlusion (RVO) or current risk factors
             for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity
             or hypercoagulability syndromes)

          -  Patients who have had chemotherapy, biologic, targeted, or radiotherapy within 4 weeks
             prior to entering the study or those who have not recovered from grade 2 and above
             adverse events due to agents administered more than 4 weeks earlier (with the
             exception of alopecia or neuropathy)

          -  History of retinal degenerative disease

          -  History of Gilbert's syndrome

          -  Previous or concurrent malignancy with the following exceptions:

               -  Adequately treated skin basal cell or squamous cell carcinoma (adequate wound
                  healing is required prior to study entry)

               -  In situ carcinoma of the cervix, treated curatively and without evidence of
                  recurrence

               -  A primary malignancy which has been completely resected and in complete remission
                  for >= 1 years

          -  Prior therapy with a MEK- inhibitor

          -  History of acute coronary syndromes (including myocardial infarction, unstable angina,
             coronary artery bypass grafting [CABG], coronary angioplasty, or stenting) < 6 months
             prior to screening

          -  Impaired cardiovascular function or clinically significant cardiovascular diseases,
             including any of the following: symptomatic chronic heart failure; evidence of
             clinically significant cardiac arrhythmias and/or conduction abnormalities < 6 months
             prior to screening except atrial fibrillation and paroxysmal supraventricular
             tachycardia

          -  Uncontrolled arterial hypertension despite appropriate medical therapy (defined as
             systolic blood pressure > 160 or diastolic blood pressure > 100)

          -  Known positive serology for human immunodeficiency virus (HIV), active hepatitis B,
             and/or active hepatitis C infection

          -  Patients who have neuromuscular disorders that are associated with elevated creatine
             kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral
             sclerosis, spinal muscular atrophy)

          -  Patients who are planning on embarking on a new strenuous exercise regimen after first
             dose of study treatment; NB: muscular activities, such as strenuous exercise, that can
             result in significant increases in plasma CK levels should be avoided while on MEK162
             treatment

          -  Impairment of gastrointestinal function or gastrointestinal disease (e.g., active
             ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome,
             small bowel resection)

          -  Any other condition that would, in the investigator's judgment, contraindicate the
             patient's participation in the clinical study due to safety concerns or compliance
             with clinical study procedures, e.g., infection/inflammation, intestinal obstruction,
             unable to swallow medication, social/ psychological issues, etc.

          -  Patients who have undergone major surgery =< 3 weeks prior to starting study drug or
             who have not recovered from side effects of such procedure

          -  Pregnant or nursing (lactating) women confirmed by a positive hCG laboratory test

          -  Women of child-bearing potential unless they are using highly effective methods of
             contraception throughout the study and for 60 days after study drug discontinuation

          -  Sexually active males unless they use a condom during intercourse while taking the
             drug and for 60 days after stopping treatment and should not father a child in this
             period; a condom is required to be used also by vasectomized men

          -  Medical, psychiatric, cognitive or other conditions that may compromise the patient's
             ability to understand the patient information, give informed consent, comply with the
             study protocol or complete the study

          -  Current grade 3 or higher neuropathy

          -  Use of other investigational drugs

          -  Known hypersensitivity to any components of the study drugs

          -  Prior intolerance to fluorouracil (5-FU) or oxaliplatin, excluding severe neuropathy
             that reversed to grade 2 or less