Erlotinib and Bevacizumab in Treating Patients With Stage IV Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: bevacizumab; erlotinib hydrochloride; fluorescence in situ hybridization; gene expression analysis; immunologic technique; laboratory biomarker analysis; biopsy
Intervention description: 10mg/kg, slow IV infusion, Days 1 and 14; 150mg PO qd; Targeting multiple genetic aberrations in isolated tumor cells.; gene expression analysis; immunologic technique; laboratory biomarker analysis; biopsy
Intervention MeSH terms: Bevacizumab; Erlotinib Hydrochloride
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: stage IV melanoma; recurrent melanoma

Summary:

      RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in
      different ways. Some block the ability of tumor cells to grow and spread. Others find tumor
      cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop
      the growth of tumor cells by blocking blood flow to the tumor. Giving erlotinib together with
      bevacizumab may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving erlotinib together with bevacizumab
      works in treating patients with stage IV melanoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Measurable Stage IV melanoma

          -  Easter Cooperative Oncology Group (ECOG) Performance Status must be 0-1

          -  Good organ function as demonstrated by, Creatinine <2.mg/dl, AST or ALT <5 times upper
             limit of normal for subjects with documented liver metastases; <2.5 times the upper
             limit of normal (ULN) for subjects without evidence of liver metastases,
             bilirubin<2.0mg/dl,, absolute neutrophil count (ANC)>1500/ul, platelets>75k/ul,
             hemoglobin (Hgb)>9 (may be transfused to obtain)

          -  Prior therapy: adjuvant interferon (IFN) allowed; no more than one prior regimen for
             advanced stage IV disease

          -  Patients must have a life expectancy of >3 months

          -  Patients with brain metastases are eligible only if they fulfill the following:
             resected or stereotactic treatment a minimum of 3 months previously and no active CNS
             disease since then; brain metastases treated greater than 6 months ago without
             evidence of progression or hemorrhage, <1cm in size per lesion (up to 3 lesions), and
             off all steroids

          -  Patients may not have received other agents, either investigational or marketed, which
             act by either EGFr inhibition or anti-angiogenesis mechanisms. Other epidermal growth
             factor receptor (EGFR) inhibitors include (but are not limited to): Iressa, erbitux,
             CI-1033. Angiogenesis inhibitors include (but are not limited to): SU5416, SU6668, SU
             0122348, CP547632, VEGF Trap, anti-integrin αVβ3.

          -  Recovered from toxicity of major surgery (4 wks), chemotherapy or biologic therapy (4
             wks), and/or radiation therapy (2 wks)

          -  No active other malignancy within 12 months

          -  No active systemic infection

          -  Over age of 18 years and signed IRB approved informed consent

        Exclusion Criteria:

          -  Subjects meeting any of the following criteria (3.2.2-3.2.16) are ineligible for study
             entry

          -  Compromised renal or hepatic function as defined by Creatinine >2.0mg/dl, aspartate
             transaminase (AST) or alanine transaminase (ALT) >5 times upper limit of normal for
             subjects with documented liver metastases; >2.5 times the upper limit of normal (ULN)
             for subjects without evidence of liver metastases

          -  Patient may not be part of any other investigational studies

          -  internationalized normal ratio (INR) > 1.5

          -  Patients with PEG or G-tube are ineligible.

          -  Major surgical procedure, open biopsy; or significant traumatic injury within 28 days,
             or anticipation of need for major surgical procedure during the course of the study

          -  Any non-healing wound, ulcer, or bone fracture.

          -  Any clinical evidence or history of a bleeding diathesis or coagulopathy.

          -  Patients with a history of deep vein thrombosis or thromboembolic disease within the
             past 6 months.

          -  History of acute myocardial infarction within 6 months. In addition, patients are
             ineligible if they have clinically significant cardiovascular disease ((e.g.,
             uncontrolled hypertension [blood pressure of >160/110 mmHg on medication], New York
             Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac
             dysrhythmia requiring medication, or peripheral vascular disease (Grade II or greater)

          -  Patients with > 1+ proteinuria will have 24-hour urine collection; for protein.
             Patients with ≥ 1gm protein/24 hrs will be excluded

          -  If child bearing age must not be pregnant or nursing and use methods to prevent
             pregnancy

          -  History or evidence upon physical examination of central nervous system (CNS) disease
             (e.g., primary brain tumor, seizures not controlled with standard medical therapy, or
             history of stroke)

          -  Inability to comply with study and/or follow-up procedures

          -  History of other disease, metabolic dysfunction, physical examination finding, or
             clinical laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that might affect the
             interpretation of the results of the study or render the subject at high risk from
             treatment complications.