BRAF Inhibitor, LGX818, Utilizing a Pulsatile Schedule in Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation
Condition: Melanoma
MeSH terms: Melanoma
Intervention: LGX818
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: LGX818; BRAF Inhibitor; Stage IV melanoma; unresectable stage III melanoma; BRAFV600 mutation; 13-053

Summary:

      The purpose of this phase II study is to find out if an investigational drug called LGX818
      can stop the melanoma from growing.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Stage IV, or unresectable stage III melanoma that harbors a BRAFV600 mutation

          -  Any prior therapy allowed except a BRAF or MEK inhibitor,.

          -  Patients must provide written informed consent prior to any screening procedures.

          -  Age 18 years or older.

          -  Willing and able to comply with scheduled visits, treatment plan and laboratory tests

          -  Patient is able to swallow and retain oral medication

          -  Measurable disease according to RECIST v1.1

          -  ECOG performance status ≤ 1

        Exclusion Criteria:

          -  Brain metastasis or leptomeningeal disease

          -  Known acute or chronic pancreatitis

          -  Prior colectomy

          -  Clinically significant cardiac disease including any of the following:

          -  CHF requiring treatment (NYHA Classification ≥ 2) in which patients have a history of
             LVEF < 45% as determined by MUGA scan or ECHO, or uncontrolled hypertension (please
             refer to WHO-ISH guidelines)

          -  History or presence of clinically significant ventricular arrhythmias or atrial
             fibrillation

          -  Clinically significant resting bradycardia

          -  Unstable angina pectoris ≤ 3 months prior to starting study drug

          -  Acute Myocardial Infarction (AMI) ≤ 3 months prior to starting study drug

          -  QTcF> 480 msec

          -  Patients with any of the following laboratory values at Screening/baseline:

          -  Absolute neutrophil count (ANC) <1,500/mm3 [1.5 x 109/L]

          -  Platelets <100,000/mm3 [100 x 109/L]

          -  Hemoglobin < 9.0 g/dL

          -  Serum creatinine>1.5 x ULN

          -  Serum total bilirubin >1.5 x ULN

          -  AST/SGOT and/or ALT/SGPT > 2.5 x ULN

          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly
             alter the absorption of oral LGX818 (e.g., ulcerative diseases, uncontrolled nausea,
             vomiting, diarrhea, malabsorption syndrome, small bowel resection).

          -  Previous or concurrent malignancy. Exceptions: adequately treated basal cell or
             squamous cell skin cancer; in situ carcinoma of the cervix, treated curatively and
             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.

          -  Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
             female after conception and until the termination of gestation, confirmed by a
             positive hCG laboratory test (> 5 mIU/mL).

        Women of child-bearing potential, defined as all women physiologically capable of becoming
        pregnant, are not allowed to participate in this study UNLESS they are using highly
        effective methods of contraception throughout the study and for 3 months after study drug
        discontinuation. Highly effective contraception methods include:

        Total abstinence or

          -  Male or female sterilization

          -  Combination of any two of the following (a+b or a+c or b+c)

               1. Use of oral, injected, or implanted hormonal methods of contraception

               2. Placement of an intrauterine device (IUD) or intrauterine system (IUS)

               3. Barrier methods of contraception: condom or occlusive cap (diaphragm or
                  cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository

                    -  Post-menopausal women are allowed to participate in this study. Women are
                       considered post-menopausal and not of child bearing potential if they have
                       had 12 months of natural (spontaneous) amenorrhea with an appropriate
                       clinical profile (e.g. age appropriate, history of vasomotor symptoms) or
                       six months of spontaneous amenorrhea with serum Follicle-Stimulating Hormone
                       (FSH) levels > 40 mIU/mL or have had surgical bilateral oophorectomy (with
                       or without hysterectomy) or tubal ligation at least six weeks prior to
                       screening. In the case of oophorectomy alone, only when the reproductive
                       status of the woman has been confirmed by follow up hormone level assessment
                       is she considered not of child bearing potential.

        Sexually active males must use a condom during intercourse while taking the drug and for 5
        T1/2 after stopping treatment and should not father a child in this period. A condom is
        required to be used also by vasectomized men in order to prevent delivery of the drug via
        seminal fluid.

        History of thromboembolic or cerebrovascular events within the last 6 months, including
        transient ischemic attack, cerebrovascular accident, deep vein thrombosis, or pulmonary
        embolism.

          -  Patients who have undergone any major surgery within the last 2 weeks prior to
             starting study drug or who would not have fully recovered from previous surgery.

          -  Known Human Immunodeficiency Virus (HIV) infection

          -  Other severe, acute, or chronic medical or psychiatric condition or laboratory
             abnormality that may increase the risk associated with study participation or study
             drug administration or that may interfere with the interpretation of study results
             and, in the judgment of the investigator, would make the patient inappropriate for the
             study.

          -  Treatment with a prior BRAF or MEK inhibitor