Axitinib in Treating Patients With Melanoma That is Metastatic or Cannot Be Removed by Surgery
Condition: Extraocular Extension Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage IIIA Intraocular Melanoma; Stage IIIA Melanoma; Stage IIIB Intraocular Melanoma; Stage IIIB Melanoma; Stage IIIC Intraocular Melanoma; Stage IIIC Melanoma; Stage IV Intraocular Melanoma; Stage IV Melanoma
MeSH terms: Melanoma; Uveal Neoplasms; Recurrence
Intervention: axitinib; laboratory biomarker analysis
Intervention description: Given PO; Correlative studies
Intervention MeSH terms: Axitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well axitinib works in treating patients with melanoma that
      has spread to other places in the body or cannot be removed by surgery. Axitinib may stop the
      growth of tumor cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically proven melanoma (including uveal) that is advanced
             (metastatic) or unresectable

          -  Measurable disease

          -  No more than two prior regimens (0-2) of systemic therapy for metastatic or recurrent
             disease; therapy (systemic or radiotherapy) administered in the neo-adjuvant or
             adjuvant setting for previously localized disease is permitted, provided it was
             completed more than 3 months prior to enrollment; palliative radiotherapy is permitted
             provided it is completed >= 2 weeks prior to study therapy initiation and there is at
             least one measurable lesion outside the radiation field; at least 2 weeks since the
             end of prior systemic treatment, radiotherapy, or surgical procedure with resolution
             of all treatment-related toxicity to National Cancer Institute (NCI) Common
             Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade =< 1 or back to
             baseline except for alopecia or hypothyroidism

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

          -  Life expectancy >= 12 weeks

          -  Absolute neutrophil count (ANC) >= 1500 cells/mm^3

          -  Platelets >= 75,000 cells/mm^3

          -  Hemoglobin >= 9.0 g/dL

          -  Creatinine =< 1.5 X upper limit normal (ULN) or calculated creatinine clearance >= 60
             mL/min

          -  Bilirubin =< 1.5 X ULN

          -  Transaminase =< 2.5 X ULN (for documented liver metastases, transaminase up to 5 X ULN
             is permitted)

          -  Random urinary protein/creatinine ratio < 2

          -  Have the ability to swallow and retain oral medication

          -  No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood
             pressure readings taken at least 1 hour apart; the baseline systolic blood pressure
             readings must be =< 140 mm Hg, and the baseline diastolic blood pressure readings must
             be =< 90 mm Hg; patients whose hypertension is controlled by antihypertensive
             therapies are eligible

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             within 3 days prior to treatment

          -  Patients of child-bearing potential must agree to use acceptable contraceptive methods
             (e.g., double barrier) during treatment and for 6 months following completion of study
             treatment

          -  Patient or legal representative must understand the investigational nature of this
             study and sign an Institutional Review Board (IRB) approved written informed consent
             form prior to receiving any study related procedure

        Exclusion Criteria:

          -  Prior anti-angiogenic therapy

          -  Major surgery < 4 weeks or radiation therapy < 2 weeks of starting the study
             treatment; prior palliative radiotherapy to metastatic lesion(s) is permitted,
             provided there is at least 1 measurable lesion that has not been irradiated

          -  Significant history of bleeding events (e.g., hemoptysis, grade 3 or grade 4 gross
             hematuria) within 6 months prior to registration

          -  Presence of serious non-healing wounds, ulcers (including gastro-intestinal) and bone
             fractures

          -  Gastrointestinal abnormalities including:

               -  Inability to take oral medication

               -  Requirement for intravenous alimentation

               -  Prior surgical procedures affecting absorption including total gastric resection;
                  segmental small bowel or colon resection is permitted

               -  Treatment for active peptic ulcer disease in the past 6 months

               -  Active gastrointestinal bleeding, unrelated to cancer, as evidenced by
                  hematemesis, hematochezia or melena in the past 6 months without evidence of
                  resolution documented by endoscopy or colonoscopy

               -  Malabsorption syndromes

               -  History of gastrointestinal (GI) perforation within prior 12 months

          -  Current use or anticipated need for treatment with drugs that are known potent
             cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors (i.e.,
             grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin,
             telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir,
             lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine)

          -  Current use or anticipated need for treatment with drugs that are known CYP3A4 or
             cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) inducers (i.e.,
             carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin,
             amobarbital, nevirapine, primidone, rifabutin, rifampin, and St. John's wort)

          -  Requirement of therapeutic anticoagulant therapy with oral vitamin K antagonists;
             low-dose anticoagulants for maintenance of patency of central venous access devise or
             prevention of deep venous thrombosis is allowed; therapeutic use of low molecular
             weight heparin (or similar parenteral drug) for venous-thromboembolic disease is
             allowed

          -  Active seizure disorder or evidence of untreated brain metastases, spinal cord
             compression, or carcinomatous meningitis; patients with brain metastases that have
             been stable for >= 4 weeks by radiographic documentation following definitive therapy
             will be permitted provided this is not the only site of metastatic disease

          -  Arterial thrombotic events within 6 months of registration, including myocardial
             infarction, unstable angina or angina requiring medical or surgical intervention in
             the past 6 months, coronary/peripheral artery bypass graft, cerebrovascular accident,
             transient ischemic attack and clinically significant peripheral vascular disease
             (i.e., claudication on less than 1 block)

          -  Current congestive heart failure (New York Heart Association [NYHA] class II, III or
             IV)

          -  Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
             (AIDS)-related illness

          -  History of a malignancy except those treated with curative intent for skin cancer
             (other than melanoma), in-situ breast or in-situ cervical cancer, or those treated
             with curative intent for any other cancer with no evidence of disease for 3 years

          -  Female patients who are pregnant or lactating

          -  Received an investigational agent within 30 days prior to enrollment

          -  A serious uncontrolled medical disorder or active infection that would impair their
             ability to receive study treatment

          -  Any condition which in the investigator's opinion would prohibit the understanding or
             rendering of informed consent and compliance with the requirements of this protocol