Bevacizumab and Sorafenib in Treating Patients With Unresectable Stage III or Stage IV Malignant Melanoma
Condition: Recurrent Melanoma; Stage III Skin Melanoma; Stage IV Skin Melanoma
MeSH terms: Melanoma; Skin Neoplasms
Intervention: Bevacizumab; Laboratory Biomarker Analysis; Pharmacological Study; Sorafenib Tosylate
Intervention description: Given IV; Correlative studies; Correlative studies; Given orally
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Sorafenib; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving bevacizumab together with sorafenib works in
      treating patients with unresectable stage III or stage IV malignant melanoma. 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. Sorafenib may stop the growth of tumor cells by
      blocking some of the enzymes needed for cell growth. Bevacizumab and sorafenib may also stop
      the growth of melanoma by blocking blood flow to the tumor. Giving bevacizumab together with
      sorafenib may kill more tumor cells.
    

Eligibility criteria:

        Criteria:

          -  No substance abuse

          -  Histologically or cytologically confirmed melanoma:

               -  Unresectable (stage III) or metastatic (stage IV) disease

          -  Measurable disease, defined as >= 1 lesion that can be accurately and serially
             measured in >= 1 dimension as >= 20 mm with conventional techniques or as >= 10 mm
             with spiral CT scan:

               -  Cutaneous lesions measuring >= 1 cm will be considered measurable disease

          -  No primary ocular melanoma

          -  No active CNS metastatic brain or meningeal tumors:

               -  Prior CNS disease allowed provided it was definitely treated >= 3 months ago AND
                  there is no CNS disease by MRI or CT scan within the past 4 weeks

               -  No residual disease

          -  Life expectancy > 12 weeks

          -  ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

          -  WBC >= 3,000/mm3

          -  Absolute neutrophil count >= 1,500/mm3

          -  Platelet count >= 100,000/mm3

          -  Bilirubin =< 1.5 times upper limit of normal (ULN)

          -  AST and ALT =< 2.5 times ULN

          -  Creatinine =< 1.5 times ULN OR creatinine clearance >= 60 mL/min

          -  Serum amylase < 1.5 times ULN OR lipase < 1.5 times ULN

          -  Urine protein:creatinine ratio < 1.0 OR urine protein < 1,000 mg by 24-hour urine
             collection

          -  No significant traumatic injury in the past 28 days

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for >= 6 months after
             completion of study treatment

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biological composition to sorafenib tosylate and bevacizumab or other agents used in
             the study

          -  No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
             human antibodies

          -  None of the following medical conditions:

        New York Heart Association class III-IV congestive heart failure; Cardiac arrhythmias,
        including atrial fibrillation if not adequately controlled; Active coronary artery disease
        or ischemia (e.g., unstable angina, cerebrovascular accident, transient ischemic attack, or
        myocardial infarction within the past 6 months); Uncontrolled hypertension

          -  None of the following medical conditions: Clinically significant peripheral vascular
             disease; Evidence of bleeding diathesis or coagulopathy

          -  No seizure disorder requiring medication (e.g., antiepileptics)

          -  No prior or concurrent cancer that is distinct in primary site or histology from the
             cancer being evaluated except cervical carcinoma in situ, treated basal cell
             carcinoma, superficial bladder tumors (Ta, Tis, or T1) or any cancer treated with
             intent to cure, rather than for palliation, < 3 years prior to study entry

          -  No more than 2 prior immunotherapy, cytokine therapy, biologic therapy, or vaccine
             therapy regimens (e.g., aldesleukin) for advanced or metastatic disease:

          -  (continued from above) Prior single-agent immunotherapy or combinations of
             immunotherapy as first treatment for advanced or metastatic disease allowed; Prior
             immunotherapy, cytokine therapy, biologic therapy, or vaccine therapy regimens in the
             adjuvant setting allowed

          -  No immunotherapy, cytokine therapy, biologic therapy, or vaccine therapy (e.g.,
             aldesleukin) for advanced or metastatic disease within the past 4 weeks

          -  No prior organ allograft or stem cell transplantation

          -  No prior Ras-pathway inhibitors (including trastuzumab [Herceptin], farnesyl
             transferase inhibitors, or MEK inhibitors)

          -  No prior treatment with a drug that targets vascular endothelial growth factor (e.g.,
             bevacizumab)

          -  No prior thalidomide or sorafenib tosylate

          -  No chemotherapy or radiotherapy within the past 4 weeks (6 weeks for nitrosoureas or
             mitomycin C) and recovered:

        Radiographic evidence of progression required for prior irradiated lesions

          -  No major surgical procedure or open biopsy within the past 28 days

          -  No Hypericum perforatum (St. John's wort) or rifampin within the past 3 weeks

          -  Concurrent full-dose anticoagulants (e.g., warfarin) with PT INR > 1.5 allowed
             provided the following criteria are met:

        Patient has an in-range INR (usually between 2 and 3) on a stable dose of oral
        anticoagulant or on a stable dose of low molecular weight heparin

          -  AND (continued from above) Patient has no active bleeding or pathological condition
             that carries a high risk of bleeding (e.g., tumor involving major vessels or known
             varices)

          -  No other concurrent investigational agents

          -  No other concurrent anticancer agents or therapies

          -  No concurrent carbamazepine, phenytoin, or phenobarbital (drugs that induce CYP450 3A
             activity)

          -  No concurrent St. John's wort or rifampin

          -  No concurrent radiotherapy

          -  No concurrent major surgery

          -  No history of or suspected HIV infection or clinically significant hepatitis B or C

          -  No serious or nonhealing wound, ulcer, or bone fracture

          -  No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
             the past 28 days

          -  No active clinically serious infections

          -  No dysphagia (difficulty swallowing)

          -  No medical, psychological, or social condition that may preclude study participation
             or evaluation of the study results