Nab-Paclitaxel and Bevacizumab or Ipilimumab as First-Line Therapy in Treating Patients With Stage IV Melanoma That Cannot Be Removed by Surgery
Condition: Metastatic Melanoma; Mucosal Melanoma; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Uveal Melanoma AJCC v7; Unresectable Melanoma
MeSH terms: Melanoma
Intervention: Bevacizumab; Ipilimumab; Laboratory Biomarker Analysis; Nab-paclitaxel; Pharmacological Study
Intervention description: Given IV; Given IV; Correlative studies; Given IV; Correlative studies
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Bevacizumab; Ipilimumab; Antineoplastic Agents, Immunological; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well nab-paclitaxel and bevacizumab or ipilimumab
      works as first-line therapy in treating patients with stage IV melanoma that cannot be
      removed by surgery. Drugs used in chemotherapy, such as nab-paclitaxel, work in different
      ways to stop the growth of tumor cells, either by killing the cells, by stopping them from
      dividing, or by stopping them from spreading. Bevacizumab may stop the growth of tumor cells
      by binding to a protein called vascular endothelial growth factor (VEGF) and by preventing
      the growth of new blood vessels that tumors need to grow. Ipilimumab blocks a substance
      called cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) on the surface of T cells and may
      help the immune system kill cancer cells. It is not yet known whether nab-paclitaxel and
      bevacizumab is more effective than ipilimumab in treating melanoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologic or cytologic proof of surgically unresectable stage IV malignant melanoma -
             including that of uveal and mucosal origin

               -  Note: biopsy can be of locoregional disease in setting of clinically evident
                  stage IV disease; a biopsy of the primary tumor alone does not fulfill this
                  requirement

          -  No more than 2 prior courses of systemic therapy for metastatic melanoma

          -  For patients with metastatic melanoma not of uveal origin, v-raf murine sarcoma viral
             oncogene homolog B1 (BRAF) V600 mutation determination using a Clinical Laboratory
             Improvement Amendments (CLIA)-approved testing method on metastatic tumor tissue

               -  NOTE: patients with metastatic melanoma of uveal origin do not need to have
                  formal BRAF testing due to low probability of a BRAF V600 mutation in their
                  metastatic tumor

          -  Measurable disease; note: disease that is measurable by physical examination only is
             not eligible

          -  Life expectancy of >= 4 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

          -  Absolute neutrophil count >=1500/mL (obtained =< 14 days prior to
             registration/randomization)

          -  Platelet count >= 100,000 x 10^9/L (obtained =< 14 days prior to
             registration/randomization)

          -  Hemoglobin >= 9 g/dL (obtained =< 14 days prior to registration/randomization)
             (patients may be transfused to meet this requirement)

          -  Creatinine =< 1.5 x upper limit of normal (ULN) (obtained =< 14 days prior to
             registration/randomization); institutional norms are acceptable

          -  Total bilirubin =< 1.5 mg/dL (obtained =< 14 days prior to registration/randomization)
             (exception: patients with documented Gilbert?s syndrome are allowed to participate
             despite elevated bilirubin)

          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =<
             2.5 x ULN and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase
             [ALT]) =< 2.5 x ULN (obtained =< 14 days prior to registration/randomization)

          -  Alkaline phosphatase =< 2.5 x ULN (obtained =< 14 days prior to
             registration/randomization); if bone metastasis is present in the absence of liver
             metastasis then =< 5 x ULN

          -  Urine dipstick for proteinuria < 2+ (obtained =< 14 days prior to
             registration/randomization) (patients discovered to have >= 2+ proteinuria on dipstick
             urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate
             =< 1 g of protein in 24 hours to be eligible)

          -  Negative serum pregnancy test done =< 7 days prior to registration/randomization, for
             women of childbearing potential only

               -  Note:

                    -  Females: adequate contraception must be used by both patient and partner
                       while receiving study drug and for 12 weeks after the last dose of study
                       drug

                    -  Males: adequate contraception must be used by both patient and partner while
                       receiving study drug; men who have a partner of childbearing age should also
                       avoid fathering a child for 6 months after the last dose of study drug

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Mayo Rochester patients only: willingness to provide mandatory blood samples for
             research purposes

        Exclusion Criteria:

          -  Brain metastases per magnetic resonance imaging (MRI) or computed tomography (CT)

               -  Note: patients who have had therapy for brain metastasis (i.e., surgical
                  resection, whole brain radiation, or stereotactic radiosurgery [SRS] even if
                  stable) are not eligible

          -  Other investigational agents =< 4 weeks prior to registration/ randomization

          -  Anti-cancer therapy (including immunotherapy) =< 4 weeks prior to
             registration/randomization; exception: adjuvant Leukine =< 14 days prior to
             registration/randomization

          -  Prior treatment in the adjuvant or metastatic setting with any of the following:

               -  Agents disrupting VEGF activity or targeting vascular endothelial growth factor
                  receptor (VEGFR);

               -  Ipilimumab;

               -  Or taxane based chemotherapy regimens (including paclitaxel, docetaxel,
                  cabazitaxel or nab-paclitaxel)

          -  Major surgical procedure, open biopsy, or significant traumatic injury =< 4 weeks
             prior to registration/randomization; (port-a-cath placement does not count as a major
             surgical procedure and patients can be enrolled at any time after placement)

          -  Fine needle aspirations or core biopsies =< 7 days prior to registration/
             randomization

          -  Planned/or anticipated major surgical procedure during the course of the study

          -  Other medical conditions including but not limited to:

               -  History of liver disease such as cirrhosis, chronic active hepatitis, chronic
                  persistent hepatitis or hepatitis B or C

               -  Active infection requiring parenteral antibiotics

               -  Poorly controlled high blood pressure (>= 150 mmHg systolic and/or 100 mmHg
                  diastolic) despite treatment

               -  New York Heart Association class II-IV congestive heart failure

               -  Serious cardiac arrhythmia requiring medication

               -  Myocardial infarction or unstable angina =< 6 months prior to
                  registration/randomization

               -  Clinically significant peripheral vascular disease

               -  Deep venous thrombosis or pulmonary embolus =< 1 year of
                  registration/randomization

               -  Ongoing need for full-dose oral or parenteral anticoagulation

               -  Ongoing anti-platelet treatment other than low-dose aspirin (i.e., aspirin 81 mg
                  by mouth daily)

               -  Active bleeding or pathological conditions that carry high risk of bleeding
                  (e.g., known esophageal varices, etc.)

               -  Serious, non-healing wound (including wounds healing by secondary intention),
                  ulcer or bone fracture

               -  History of abdominal fistula, gastrointestinal perforation or intra-abdominal
                  abscess =< 6 months prior to registration/randomization

               -  History of central nervous system (CNS) disease (e.g., vascular abnormalities,
                  etc.), clinically significant stroke or transient ischemic attack (TIA) =< 6
                  months prior to registration/randomization, seizures not controlled with standard
                  medical therapy

               -  Radiographically documented tumor invading major blood vessels

               -  History of hypertensive crisis or hypertensive encephalopathy

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Men and women of reproductive potential who are not using effective birth control
                  methods Note: women of childbearing potential must have a negative serum
                  pregnancy test =< 7 days prior to registration/randomization; adequate
                  contraception must be used while receiving study drug and for 12 weeks after the
                  last dose of study drug, by both women and men and by both patient and partner;
                  men who have a partner of childbearing potential should also avoid fathering a
                  child for 6 months after the last dose of study drug

          -  Existence of peripheral sensory neuropathy >= grade 2 (from any cause)

          -  History of other malignancy =< 5 years with the exception of basal cell or squamous
             cell carcinoma of the skin, treated with local resection only, or carcinoma in situ
             (e.g. of the cervix, breast, prostate, etc.)

          -  Radiation therapy (other than palliative) =< 2 weeks prior to randomization; note:
             patients who have had > 25% of their functional bone marrow irradiated are not
             eligible for this trial

          -  Active or recent history of hemoptysis (>= 1/2 teaspoon of bright red blood per
             episode) =< 30 days prior to registration/randomization

          -  Known hypersensitivity to any of the components of ipilimumab, bevacizumab, or
             nab-paclitaxel

          -  History of inflammatory bowel disease (e.g., Crohn?s, ulcerative colitis) - note
             patients with irritable bowel syndrome are eligible

          -  Diagnosis of autoimmune disease (i.e., rheumatoid arthritis, scleroderma, systemic
             lupus erythematosus [SLE], autoimmune vasculitis, Guillain-Barre syndrome, etc.),
             regardless if patient is currently receiving treatment at time of
             registration/randomization

          -  Systemic corticosteroids use =< 2 weeks, regardless of indication; note: patients who
             are on inhaled corticosteroids are eligible