Clinical trial NCT01072175 (phase 2, status: completed)
Conditions: cancer
ICD codes: C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2
Drugs: gsk2118436, gsk1120212
SMILES: CC(C)(C)C1=NC(=C(S1)C1=NC(N)=NC=C1)C1=C(F)C(NS(=O)(=O)C2=C(F)C=CC=C2F)=CC=C1, CN1C(=O)C(C)=C2N(C(=O)N(C3CC3)C(=O)C2=C1NC1=CC=C(I)C=C1F)C1=CC(NC(C)=O)=CC=C1
Eligibility criteria:

        Key Inclusion Criteria:

          -  Capable of given written informed consent, which includes compliance with the
             requirements and restrictions listed in the consent form.

          -  Male or female age 18 years or greater; able to swallow and retain oral medication.

          -  BRAF mutation positive melanoma or colorectal cancer; other BRAF mutation positive
             tumor types may be considered.

          -  Measurable disease according to RECIST version 1.1.

          -  Eastern Cooperative Oncology Group Performance Status of 0 or 1 for Parts A and B.
             Subjects with Eastern Cooperative Oncology Group Performance Status of 2 or less may
             be entered into Part C with approval of medical monitor.

          -  Agree to contraception requirements.

          -  Calcium phosphorus product less than 4.0mmol2/L2.

          -  Adequate organ system function.

        Key Exclusion Criteria:

          -  Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or
             biologic therapy).

          -  Part A and Part B: Prior exposure to BRAF or MEK inhibitors unless approved by the GSK
             Medical Monitor.

          -  Part C: Prior exposure to BRAF or MEK inhibitors. Prior anti-cancer therapy in the
             metastatic setting, with the exception of up to one regimen of chemotherapy and/or
             interleukin-2 (IL-2).

          -  Part D: Prior exposure to BRAF inhibitors. A washout period of 6 weeks is required for
             ipilimumab.

          -  Received an investigational anti-cancer drug within 4 weeks or 5 half-lives (whichever
             is shorter) of study drug administration--- at least 14 days must have passed between
             the last dose of prior investigational anti-cancer drug and the first dose of study
             drug.

          -  Current use of a prohibited medication or requires any of these medications during
             treatment with study drug.

          -  Current use of therapeutic warfarin.

          -  Any major surgery, radiotherapy, or immunotherapy within the last 4 weeks. Limited
             radiotherapy within the last 2 weeks.

          -  Chemotherapy regimens with delayed toxicity within the last 4 weeks. Chemotherapy
             regimens given continuously or on a weekly basis with limited potential for delayed
             toxicity within the last 2 weeks.

          -  Unresolved toxicity greater than National Cancer Institute-Common Terminology Criteria
             for Adverse Events version 4 Grade 1 from previous anti-cancer therapy except
             alopecia.

          -  History of retinal vein occlusion, central serous retinopathy or glaucoma.

          -  Predisposing factors to retinal vein occlusion including uncontrolled hypertension,
             uncontrolled diabetes, uncontrolled hyperlipidemia, and coagulopathy.

          -  Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk
             factor for retinal vein occlusion or central serous retinopathy.

          -  Intraocular pressure greater than 21mm Hg as measured by tonography.

          -  Glaucoma diagnosed within one month prior to study Day 1.

          -  Presence of active gastrointestinal disease or other condition that will interfere
             significantly with the absorption, distribution, metabolism or excretion of drugs.

          -  Known human immunodeficiency virus, Hepatitis B or Hepatitis C infection.

          -  Primary malignancy of the central nervous system.

          -  Untreated or symptomatic brain metastasis, leptomeningeal disease or spinal cord
             compression. Subjects who are on a stable dose of corticosteroids for more than 1
             month or off corticosteroids for 2 weeks can be enrolled with approval of medical
             monitor. Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs.

          -  Subjects with brain metastases are excluded, unless

             a. All known lesions must be previously treated with surgery or stereotactic
             radiosurgery, and- b. Brain lesion(s), if still present, must be confirmed stable
             (i.e. no increase in lesion size) for ≥90 days prior to first dose on study (must be
             documented with two consecutive MRI or CT scans using contrast), and c. Asymptomatic
             with no corticosteroids requirement for ≥ 30 days prior to first dose on study, and d.
             No enzyme-inducing anticonvulsants for ≥ 30 days prior to first dose on study.

          -  History of alcohol or drug abuse within 6 months prior to screening.

          -  Psychological, familial, sociological or geographical conditions that do not permit
             compliance with the protocol.

          -  QTc interval greater than or equal to 480msecs.

          -  History of acute coronary syndromes (including unstable angina), coronary angioplasty,
             or stenting within the past 24 weeks.

          -  Class II, III, or IV heart failure as defined by the New York Heart Association
             functional classification system.

          -  Abnormal cardiac valve morphology (subjects with minimal abnormalities can be entered
             on study with approval from the medical monitor.

          -  Treatment refractory hypertension defined as a blood pressure of systolic> 140 mmHg
             and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy

          -  Patients with intra-cardiac defibrillators or permanent pacemakers.

          -  Cardiac metastases

          -  Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to the study drugs or excipients.

          -  Pregnant or lactating female.

          -  Unwillingness or inability to follow the procedures required in the protocol.

          -  Uncontrolled diabetes, hypertension or other medical conditions that may interfere
             with assessment of toxicity.

          -  Subjects with known glucose 6 phosphate dehydrogenase deficiency.