Phase I of Histone Deacetylase (HDAC) Inhibitor Panobinostat With Ipilimumab With Unresectable III/IV Melanoma
Condition: Melanoma; Skin Cancer
MeSH terms: Melanoma
Intervention: Panobinostat; Ipilimumab
Intervention description: Participants will be assigned to receive a certain dose of panobinostat (5, 10, 15, or 20 mg). The dose of panobinostat will depend on the time point the participant enters the study and the side effects of other participants already on the study.; Dose of ipilimumab of 3 mg per kg (mg/kg) of body weight.
Intervention MeSH terms: Ipilimumab; Panobinostat
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Stage III Melanoma; Stage IV Melanoma; HDAC Inhibitor

Summary:

      The purpose of this study is to find out if an investigational drug called panobinostat can
      be given safely with another drug called ipilimumab. Investigators want to learn more about
      the side effects of this combination of drugs using different doses of panobinostat and the
      same dose of ipilimumab.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women ≥ 18 years old

          -  Participants must be ipilimumab naïve with progressive unresectable Stage III or Stage
             IV melanoma who are either treatment naïve or may have been treated with up to 3 prior
             treatments for melanoma (e.g., chemotherapy, biologic or targeted therapy or IL-2).

          -  Histologic or cytologic confirmation of stage III or stage IV melanoma

          -  Measurable disease at baseline as assessed by CT and/or MRI

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Screening laboratory values must meet the following criteria: white blood count (WBCs)
             ≥ 2000/μL; Neutrophils ≥ 1500/μL; Platelets ≥ 100 x 10^3/μL; Hemoglobin ≥ 9.0 g/dL;
             Creatinine Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine
             clearance > 40 mL/minute (using Cockcroft/Gault formula); aspartic transaminase (AST)
             ≤ 3 x ULN; alanine transaminase (ALT) ≤ 3 x ULN; Total Bilirubin ≤ 1.5 x ULN (except
             those with Gilbert Syndrome who must have total bilirubin < 3.0 mg/dL)

          -  Men and women of childbearing potential (WOCBP) must be using an acceptable method of
             contraception to avoid pregnancy throughout the study and for at least 12 weeks after
             the last dose of investigational product in such a manner that the risk of pregnancy
             is minimized. Women must have a negative serum pregnancy test within 72 hours prior to
             the start of investigational product.

        Exclusion Criteria:

          -  Known or suspected brain metastasis, or brain as the only site of disease, with the
             following exceptions: controlled brain metastasis (no radiographic progression at
             least 4 weeks following radiation and/or surgical treatment, off steroids for at least
             4 weeks, and have no new or progressing neurological signs or symptoms); history of
             prior malignancy with the exception of carcinoma in situ of the cervix or other
             malignancy diagnosed > 2 years ago that has undergone potentially curative therapy
             with no evidence of disease for the last ≥ 2 years and that is deemed by the
             investigator to be at a low risk of recurrence

          -  Active autoimmune disease or a history of known or suspected autoimmune disease with
             the exception of subjects with isolated vitiligo, treated thyroiditis or resolved
             childhood asthma/atopy

          -  Known human immunodeficiency virus (HIV), active hepatitis A, or hepatitis B or C
             infection

          -  History of any hepatitis (e.g., alcohol or non-alcohol steatohepatitis (NASH), drug-
             related, autoimmune)

          -  Evidence of active infection that requires anti-bacterial, anti-viral, or anti-fungal
             therapy ≤ 7 days prior to initiation of study drug therapy

          -  History of acute diverticulitis, or current chronic diarrhea

          -  Active peptic ulcer disease even if asymptomatic

          -  History of adrenal insufficiency (including subjects using replacement therapy)

          -  Prior organ allograft or allogeneic bone marrow transplantation

          -  Uncontrolled or significant cardiovascular disease including, but not limited to, any
             of the following: Myocardial infarction within the past 6 months; Uncontrolled angina
             within the past 6 months; Any history of clinically significant ventricular
             arrhythmias (such as ventricular tachycardia, ventricular fibrillation or Torsades de
             pointes). Controlled atrial fibrillation by itself is not an exclusion criterion.;
             Baseline corrected QT interval (QTc) interval greater than 500 milliseconds

          -  Baseline toxicities from prior anti-cancer treatments > Grade 1

          -  Inability to be venipunctured and/or tolerate venous access

          -  Any major surgery within 4 weeks or a diagnostic procedure (e.g. incision, needle
             biopsy) within 1 day of study drug administration

          -  Any current or recent (within 3 months) gastrointestinal disease that could
             potentially impact the ability to swallow and/or absorb study drug (i.e.,
             gastrointestinal surgery, malabsorption syndrome)

          -  Diabetes mellitus uncontrolled by medication

          -  Known drug or alcohol abuse

          -  Presence of underlying medical condition that in the opinion of the Investigator or
             Sponsor could adversely affect the ability of the subject to comply with or tolerate
             study procedures and/or study therapy, or confound the ability to interpret the
             tolerability of combined administration of panobinostat and ipilimumab in treated
             subjects

          -  History of allergy to components of ipilimumab or panobinostat, or known allergy to
             other antibody therapies.

          -  WOCBP who are unwilling or unable to use an acceptable method to minimize the risk of
             pregnancy for the entire study period and for at least 12 weeks after the last dose of
             investigational product

          -  Women who are pregnant or breastfeeding

          -  Women with a positive pregnancy test on enrollment or prior to investigational product
             administration

          -  Sexually active fertile men not using effective birth control if their partners are
             WOCBP

          -  Exposure to any investigational drug within 4 weeks of study drug administration.

          -  Any anti-cancer therapy (e.g., chemotherapy, biologics, radiotherapy, or hormonal
             treatment) within 4 weeks or at least 5 half-lives (whichever is longer) of study drug
             administration

          -  Prior therapy with an anti-CTLA4 antibody or an HDAC inhibitor

          -  Concurrent chemotherapy, hormonal therapy, immunotherapy regimens, or radiation
             therapy, standard or investigational

          -  Prisoners or subjects who are involuntarily incarcerated

          -  Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (e.g., infectious disease) illness