Clinical trial NCT01519427 (phase 2, status: terminated)
Conditions: recurrent melanoma, stage iiia melanoma, stage iiib melanoma, stage iiic melanoma, stage iv melanoma
ICD codes: G47.13, J01.41, K11.22, K12.0, N96, F33.8, G03.2, C43.0, C43.31, D03.9, C43.51, C43.9, D03.0, C43.4, C43.0, C43.31, D03.9, C43.51, C43.9, D03.0, C43.4, C43.0, C43.31, D03.9, C43.51, C43.9, D03.0, C43.4, C43.0, C43.31, D03.9, C43.51, C43.9, D03.0, C43.4
Drugs: akt inhibitor mk2206, selumetinib
SMILES: CN1C=NC2=C1C=C(C(O)=NOCCO)C(NC1=C(Cl)C=C(Br)C=C1)=C2F
Reason stopped: 
    study terminated due to slow accrual
  
Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have incurable unresectable stage III or IV histologically confirmed
             Melanoma with V600-mutant BRAF disease and must have progressed after therapy on
             selective BRAF inhibitor; all patients must have biopsiable tumor and a biopsy must be
             performed with the collection of FFPE and if possible FF prior to initiation of
             treatment on this protocol; archival tumor tissue must also be obtained if at all
             available; this required biopsy will not be necessary if a previous biopsy of
             progressing tumor after selective BRAF therapy had already been obtained and is
             adequate

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded for
             non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm with conventional
             techniques or as ≥ 10 mm with spiral computed tomography (CT) scan

          -  Patients must have received prior therapy and progressed following a selective BRAF
             inhibitor (i.e., vemurafenib, dabrafenib, LGX818, etc.); patients must have completed
             prior therapy a minimum of 4 weeks previously (6 weeks for BCNU and/or mitomycin C), 4
             weeks for prior biologic therapy, and 2 weeks for localized radiation therapy; all
             treatment related toxicity must have resolved to grade 2 or less as well; patients may
             initiate the protocol treatment at 48 hours following the completion of BRAF
             inhibitor; patients must have had no more than 2 prior chemotherapy regimens; patients
             cannot receive chemotherapy after the BRAF inhibitor treatment and prior to enrollment
             on this protocol; up to two prior immunotherapy regimens for advanced disease are
             allowed and one may be given between BRAF inhibitor therapy and this trial

          -  Patients must not be refractory to the BRAF inhibitor; patients must demonstrate some
             degree of tumor regression initially on BRAF inhibitor prior to progression; (tumor
             regression does not require RECIST objective response); they cannot have progressive
             disease at the time of first evaluation (4 or 8 weeks) on the BRAF inhibitor

          -  Baseline Ophthalmologic exam must be done at screening to include slit lamp exam and
             fundoscopy; an OCT scan should be considered in case of retinal abnormality at exam

          -  Life expectancy of greater than or equal to 3 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤1 (Karnofsky ≥ 70%)

          -  Absolute neutrophil count ≥ 1,500 mm³

          -  Hemoglobin ≥ 9.0 g/dL (patients may be transfused to achieve level)

          -  Platelet count ≥ 100,000/μL

          -  Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate
             transaminase(SGPT) < 2.5 X upper limit of normal (ULN)

          -  Total bilirubin < 1.5 mg/dL

          -  Serum creatinine ≤ 2.0 mg/dL OR creatinine clearance > 50 mL/min, determined by
             24-hour urine collection

          -  Fasting blood glucose < 160 mg/dL OR

          -  HgbA1C < 8% disease (uncontrolled diabetes)

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation

          -  Patients must have a negative serum pregnancy test prior to being eligible to take
             part in the study

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with AZD6244 hydrogen sulfate and MK-2206

          -  Baseline echocardiogram or MUGA must be performed at screening and patients must have
             LVEF > 55%; additionally baseline EKG must be performed and corrected QTc must be <
             480 milliseconds

          -  Baseline electrocardiogram(EKG) must be performed and corrected QTc must be < 480
             milliseconds

          -  Patients must be able to swallow tablets and capsules to participate in the study

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to AZD6244 hydrogen sulfate, MK-2206, or other agents used in the
             study

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, Uncontrolled intercurrent illness including, but not limited to, ongoing or
             active infection, psychiatric illness/social situations that would limit compliance
             with study requirements, symptomatic congestive heart failure, unstable angina
             pectoris, cardiac arrhythmia, uncontrolled hypertension (BP >= 150/95 despite optimal
             therapy), baseline ejection fraction < 55% or the lower limit of institutional normal,
             heart failure NYHA Class II or above, prior or current cardiomyopathy, atrial
             fibrillation with heart rate > 100 bpm, and uncontrolled angina (Canadian
             Cardiovascular society grade II-IV despite medical therapy); acute coronary syndrome
             within 6 months from starting therapy

          -  Patients must have completed prior therapy a minimum of 4 weeks previously (6 weeks
             for BCNU and/or mitomycin C), 4 weeks for prior biologic therapy, and 2 weeks for
             localized radiation therapy

          -  All treatment-related toxicity must have resolved to grade 2 or less

          -  No patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier

          -  Patients must have had no more than 2 prior chemotherapy regimens

          -  Patients cannot receive chemotherapy after the BRAF-inhibitor treatment and prior to
             enrollment on this protocol

          -  Up to two prior immunotherapy regimens for advanced disease are allowed and one may be
             given between BRAF-inhibitor therapy and this trial

          -  Patients may not be receiving any other investigational agents at the same time as
             study treatment

          -  Patients receiving medications or substances that are strong inhibitors or inducers of
             cytochrome P450 3A4 (CYP3A4) are ineligible

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible

          -  Patients must not have received chemotherapy in the time between the failure of BRAF
             inhibitor and the enrollment onto the present trial