Lenalidomide (Revlimid) to Treat Advanced Ocular Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Revlimid
Intervention description: oral dose (1 capsule) 25 mg per day 7 days a week for cohort 1 oral dose (1 capsule) 5 mg per day 7 days a week for cohort 2
Intervention MeSH terms: Lenalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Response Rate; Toxicity; Progression-Free Survival; Overall Survival; Pharmacokinetic; Ocular Melanoma

Summary:

      This study will test whether an experimental drug called Revlimid (lenalidomide) can reduce
      tumor size and prolong survival in patients with metastatic melanoma (melanoma that has
      spread beyond the original tumor site). It will also examine the toxicity and blood effects
      of Revlimid.

      Patients 18 years of age and older with stage IV ocular melanoma may be eligible for this
      study. Candidates are screened with a medical history and physical and examination, blood and
      urine tests, electrocardiogram, chest x-ray, computed tomography (CT) scan and other imaging
      scans if needed, such as a bone scan, magnetic resonance imaging (MRI), ultrasound, or
      positron emission tomography (PET).

      Participants are admitted to the National Institutes of Health (NIH) Clinical Center for 24
      hours for their first oral dose of Revlimid. During the hospital stay, blood is drawn before
      the dose is given and again at 0.25, 0.5, 1, 2, 4, 6, 9, 12 and 24 hours after dosing to see
      how the body handles the drug. If the drug is well tolerated, patients are sent home with a
      21-day supply of drug to take once a day for 21 days, then go off drug 7 days. This regimen
      constitutes one 28-day treatment cycle. Treatment cycles may continue for up to 2 years.

      Patients keep a daily diary of side effects and have blood drawn once a week. The drug dose
      may be adjusted according to the laboratory test results. If unacceptable toxicity occurs,
      treatment may be stopped.

      Patients who agree to be biopsied undergo this procedure before treatment begins and at the
      end of treatment cycles 3 and 6. A small area of skin is numbed with medicine and a small
      piece of tumor is removed with a needle or by a small cut in the tumor. The tissue is
      examined under a microscope.

      Patients return to NIH after the first month of treatment and then every 3 months to evaluate
      their tumors and treatment of side effects. The visits include a physical examination, x-rays
      and scans to evaluate tumors. Visits are scheduled every 3 months while on treatment; then
      every 3 months for 2 years afterwards; then every 4 months for 1 year; and as needed after
      that. Patients will have a brain magnetic resonance imaging scan once a year to watch for new
      tumor areas.
    

Eligibility criteria:

        -INCLUSION CRITERIA:

          1. All patients with stage IV ocular melanoma, who have measurable disease will be
             considered.

          2. Patients must have histopathological documentation of ocular melanoma confirmed in the
             Laboratory of Pathology/National Cancer Institute (NCI) of the Clinical Center at the
             National Institutes of Health. This can be from tissue obtained outside the National
             Institutes of Health (NIH).

          3. Patient must be Eastern Cooperative Oncology Group (ECOG) performance status of less
             than or equal to 2.

          4. Patients must have a life expectancy of more than 3 months.

          5. Hematological eligibility parameters (prescreen):

               -  Granulocyte count greater than 1,500/mm^3

               -  Platelet count greater than 100,000/mm^3

               -  If the creatinine is greater than 1.5 mg/dL, obtain a 24 hour urine collection.
                  Creatinine clearance must be greater than 60 mL/min/1.73m^2.

               -  Hepatic function: bilirubin (total) less than or equal to 2.0 mg/dl; Alanine
                  aminotransferase (ALT) less than 10 x upper limit of normal; Aspartate
                  aminotransferase (AST) less than 10 x upper limit of normal.

          6. Patients must have recovered from any acute toxicity related to prior therapy or
             surgery, to a grade 1 or less unless specified above.

          7. Patients must not have had prior surgery, chemotherapy, hormonal therapy, radiation
             therapy, or biological therapy, for at least 4 weeks prior to starting study
             medication. Patients who were receiving mitomycin C, nitrosoureas, or carboplatin must
             be 6 weeks from the last administration of chemotherapy.

          8. Patients must not have an acute, critical illness, including a serious untreated
             infection.

          9. Patients must be willing to return to the National Institutes of Health (NIH) for
             follow-up visits.

         10. All patients who are sexually active and able to conceive will be required to use
             contraception during treatment with lenalidomide.

        Only two criteria are allowed by the Food and Drug Administration (FDA) for the status of
        not of child bearing potential: hysterectomy or menopause for 24 consecutive months. Women
        of child bearing potential will be required to use two methods of birth control, one highly
        effective method and one additional method, at the same time during treatment and for one
        month after the completion of lenalidomide treatment. These methods must be used for at
        least four weeks before starting lenalidomide, during treatment, and for at least four
        weeks following the last dose of lenalidomide. Acceptable forms of birth control include:

        Intrauterine device (IUD)

        Latex condom

        Hormonal (Birth control pills, injections, implants)

        Diaphragm

        Tubal Ligation

        Cervical cap

        Partner's vasectomy

        Two barrier methods may be used if the physician agrees that the highly effective methods
        are medically contraindicated.

        Women of childbearing potential must have a negative urine pregnancy test 24 hours prior to
        the start of lenalidomide.

        Men who are sexually active must agree to use latex condoms.

        Patients must be able to understand and sign informed consent form.

        Patients must be greater than or equal to 18 years of age.

        EXCLUSION CRITERIA:

          1. Patients with evidence of active brain metastases will be excluded. Patients must have
             had a complete excision or radiotherapy and remain asymptomatic with stable disease as
             shown by magnetic resonance imaging (MRI) for at least six months.

          2. Patients who are pregnant or lactating. No data is currently available about the
             excretion of lenalidomide in breast milk. Although no preclinical data suggest
             teratogenicity with this compound, because of the relationship to thalidomide, we will
             exclude patients who are pregnant or lactating.

          3. Patients with a history of unstable or newly diagnosed angina pectoris, recent
             myocardial infarction (within 6 months of enrollment), New York class II-IV congestive
             heart failure, chronic obstructive lung disease requiring oxygen therapy or
             uncontrolled seizure activity are not eligible.

          4. Patients who are known positive for human immunodeficiency virus (HIV) as it may
             increase their risk of infection since lenalidomide has effects on cells involved in
             the immune system.

          5. Patients who have had prior therapy with lenalidomide.

          6. Patients with known hypersensitivity reaction to lenalidomide.