Bevacizumab and Temozolomide or Bevacizumab and Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Carboplatin in Treating Patients With Stage IV Malignant Melanoma That Cannot Be Removed by Surgery
Condition: Melanoma (Skin)
MeSH terms: Melanoma
Intervention: bevacizumab; carboplatin; paclitaxel albumin-stabilized nanoparticle formulation; temozolomide
Intervention description: Given IV over 30-90 minutes; Given IV over 30 minutes; Given IV over 30 minutes; Oral temozolomide on days 1-5
Intervention MeSH terms: Paclitaxel; Bevacizumab; Carboplatin; Temozolomide; Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 95.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IV melanoma

Summary:

      RATIONALE: Drugs used in chemotherapy, such as temozolomide, paclitaxel albumin-stabilized
      nanoparticle formulation, and carboplatin, work in different ways to stop the growth of tumor
      cells, either by killing the cells or by stopping them from dividing. 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. It is not yet known whether bevacizumab is more effective
      when given together with temozolomide or paclitaxel albumin-stabilized nanoparticle
      formulation and carboplatin in killing malignant melanoma cells.

      PURPOSE: This randomized phase II trial is studying the side effects of giving temozolomide
      together with bevacizumab and to see how well it works compared with giving bevacizumab
      together with paclitaxel albumin-stabilized nanoparticle formulation and carboplatin in
      treating patients with stage IV malignant melanoma that cannot be removed by surgery.
    

Eligibility criteria:

        -  Histologic confirmed diagnosis of malignant melanoma

               -  Stage IV disease

               -  Not amenable tosurgery

          -  Measurable disease with at least one lesion whose longest diameter canbe measured as ≥
             20 mm by CT or MRI scans OR ≥ 10 mm by spiral CT

               -  No disease that is measurable by physical examination only

          -  No brain metastases per MRI or CT

          -  No radiographically documented invasion of adjacent organs(duodenum, stomach, etc.) or
             tumor invading major blood vessels

          -  ECOG performance status 0-1

          -  Life expectancy ≥ 4 months

          -  ANC ≥ 1,500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Hemoglobin ≥ 9 g/dL (transfusion allowed)

          -  Creatinine ≤ 1.5 times upper limit of normal (ULN)

          -  Total bilirubin ≤ 1.5 mg/dL (unless Gilbert syndrome)

          -  AST ≤ 2.5 times ULN

          -  Alkaline phosphatase ≤ 2.5 times ULN

          -  Urine protein:creatinine ratio < 1.0 at screening ORproteinuria < 2+ by urine dipstick
             or protein ≤ 1 g by 24-hour urine collection

          -  Negative serum pregnancy test

          -  Not pregnant or nursing

          -  Fertile patients must use effective contraception

          -  Active infection requiring parenteral antibiotics

          -  Poorly controlled high blood pressure (≥ 150 mm Hg systolic and/or100 mm Hg diastolic)
             despite treatment

          -  NYHA class II-IV congestive heart failure

          -  Serious cardiac arrhythmia requiring medication

          -  Myocardial infarction or unstable angina within the past 6 months

          -  Clinically significant peripheral vascular disease

          -  Deep venous thrombosis or pulmonary embolus within the past year

          -  Active bleeding or pathological conditions that carry high risk of bleeding (e.g.,
             known esophageal varices)

          -  Serious, non-healing wound (including wounds healing by secondary intention), ulcer or
             bone fracture

          -  Abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within the
             past 6 months

          -  History of CNS disease (e.g., primary brain tumor, vascular abnormalities, etc.)

          -  Clinically significant stroke or TIA within the past 6 months

          -  Seizures not controlled with standardmedical therapy

          -  Peripheral neuropathy ≥ grade 2

          -  History of other malignancy within the past 5 years except basal cell or squamous cell
             carcinoma of the skin treatable with local resection only or carcinoma in situ of the
             cervix

          -  Significant traumatic injury within the past 4 weeks

          -  History of hypertensive crisis or hypertensive encephalopathy

          -  Active or recent (≤ 30 days) history of hemoptysis (≥ ½ teaspoon of bright red blood
             per episode)

          -  Known hypersensitivity to any of the components of bevacizumab

          -  Known to be HIV positive

          -  Current or known history of hepatitis

          -  Prior adjuvant chemotherapy and/or immunotherapy for this cancer allowed

          -  No prior treatment with agents disrupting VEGF activity (i.e., bevacizumab,VEGF-trap,
             anti-VEGFR Mab)

          -  No ongoing need for full-dose oral or parenteral anticoagulation

          -  No ongoing anti-platelet treatment other than low-dose aspirin(i.e., aspirin 81 mg
             daily)

          -  No other investigational agents within the past 4 weeks

          -  No major surgical procedure or open biopsy within the past 4 weeks

          -  No fine needle aspirations or core biopsies within the past 7 days

          -  No prior chemotherapy in the metastatic setting

          -  No prior treatment with sunitinib malate or sorafenib

          -  No prior treatment with any taxane-based chemotherapy

          -  Patients who have had > 25% of their functional bone marrow irradiated are not
             eligible for this trial

          -  No adjuvant radiation therapy within the past 4 weeks

          -  More than 2 weeks since prior and no concurrent palliative radiation therapy

          -  No concurrent major surgical procedure

          -  No concurrent participation in another clinical study for procedures or agents that
             treat the same primary study malignancy