Crizotinib in High-Risk Uveal Melanoma Following Definitive Therapy
Condition: Uveal Melanoma
MeSH terms: Melanoma; Uveal Neoplasms
Intervention: Crizotinib
Intervention description: An anti-cancer drug acting as an anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) inhibitor, used to treat non-small cell lung cancer (NSCLC) that has spread to other parts of the body and is caused by a defect in a gene called ALK.
Crizotinib will be provided as capsules containing 200 or 250 mg of study medication for oral administration.
Intervention MeSH terms: Crizotinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Crizotinib; 14-063

Summary:

      The study is designed to determine the 32 month rate of distant relapse in patients with
      uveal melanoma who are at high risk of recurrence following definitive therapy with surgery
      or radiation who receive adjuvant crizotinib; and secondarily, the overall survival and
      disease specific survival in this patient population.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Primary diagnosis of uveal melanoma at least 12 mm in largest basal diameter as
             clinically determined by the treating investigator. Cytologic determination of
             diagnosis is not required. Size is based on clinical assessment (e.g. by ultrasound or
             direct ophthalmoscopy) prior to enucleation or radiation therapy.

          -  Definitive therapy of the primary uveal melanoma must have been performed within 90
             days of initiating protocol therapy.

          -  High-risk (class 2) uveal melanoma as determined by gene expression profiling

          -  No evidence of metastatic disease.

          -  Age ≥18 years.

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (Karnofsky ≥ 70%.

          -  Life expectancy of greater than 3 months.

          -  Able to swallow and retain orally-administered medication and does not have any
             clinically significant gastrointestinal abnormalities that may alter absorption such
             as malabsorption syndrome or major resection of the stomach or bowels

          -  Patients must have normal organ and marrow function as defined below:

          -  Absolute neutrophil count (ANC) >1,000 cells/mm³

          -  Platelet count >75,000/mm³

          -  Hemoglobin >9.0g/dL

          -  Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) <3x upper
             limited of normal (ULN)

          -  Total bilirubin <2x ULN

          -  Alkaline phosphatase <3x ULN

          -  Serum creatinine <2x ULN or a creatinine clearance > 60mL/min

          -  Note: Patients with hyperbilirubinemia clinically consistent with an inherited
             disorder of bilirubin metabolism (e.g., Gilbert syndrome) will be eligible at the
             discretion of the treating physician and/or the principal investigator.

          -  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 until 4 months after completion of crizotinib
             administration. Women of child-bearing potential must have a negative serum pregnancy
             test within 14 days prior to study entry. Should a woman become pregnant or suspect
             she is pregnant while she or her partner is participating in this study, she should
             inform her treating physician immediately. Men treated or enrolled on this protocol
             must also agree to use adequate contraception prior to the study, for the duration of
             study therapy, and 4 months after completion of crizotinib administration.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  History of another malignancy except for those who have been disease-free for 3 years,
             or patients with a history of completely resected non-melanoma skin cancer and/or
             patients with indolent secondary malignancies not requiring active therapy, are
             eligible. Consult the study Principal Investigator if unsure whether second
             malignancies meet the requirements specified above.

          -  Any major surgery or extensive radiotherapy (except that which is required for
             definitive treatment of primary uveal melanoma), chemotherapy with delayed toxicity,
             biologic therapy, or immunotherapy within 21 days prior to initiation of study
             therapy.

          -  History of prior crizotinib use.

          -  Use of other investigational drugs within 28 days (or five half-lives, whichever is
             shorter; with a minimum of 14 days from the last dose) preceding the first dose of
             study therapy and during the study.

          -  Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to crizotinib.

          -  Concurrent administration of crizotinib and a strong inhibitor or inducer of CYP3A is
             not permitted. Many over-the-counter and dietary supplements also inhibit or induce
             CYP3A and thus are prohibited.

          -  A QT interval corrected for heart rate using the Bazett's formula QTcB ≥ 480 msec.

          -  Concurrent administration of crizotinib and agents that can cause QTc prolongation is
             not permitted.

          -  Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C
             Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection,
             which will be allowed). HIV-positive patients on combination antiretroviral therapy
             are ineligible because of the potential for pharmacokinetic interactions with
             crizotinib. In addition, these patients are at increased risk of lethal infections
             when treated with marrow-suppressive therapy.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.