Combined BRAF-Targeted Therapy & Immunotherapy for Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Aldesleukin; Vemurafenib
Intervention description: Intravenous therapy given every 8 hours for up to 14 doses per week.; Tablets given twice daily.
Intervention MeSH terms: Aldesleukin; Interleukin-2; Vemurafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic; Unresectable; V600E mutation

Summary:

      This research study is a Phase II clinical trial of an investigational combination of drugs
      (vemurafenib and aldesleukin) to learn whether the combination works in treating a specific
      cancer. While both vemurafenib and aldesleukin are approved by the FDA for the treatment of
      metastatic melanoma, the FDA has not yet approved the combination of vemurafenib and
      aldesleukin.

      Researchers have found that a large number of melanoma cells have mutations in the BRAF gene.
      It has been shown that vemurafenib blocks the effects of these mutations in the BRAF gene,
      and, as a result, may help to prevent cancer growth.

      Aldesleukin, also referred to as IL-2, is an immunotherapy drug administered via IV infusion
      that increases the growth of key cells within the immune system that are responsible for
      targeting cancer cells. Activating more of these key cells, called T-lymphocytes and
      natural-killer cells, leads to increased cancer cell death.

      The BRAF gene is located on a larger pathway called the MAPK pathway. Studies have shown that
      when a BRAF inhibitor, like vemurafenib is used to block the MAPK pathway, melanocytes, or
      cancer cells express more proteins on their surfaces, making them easier for T-lymphocytes
      and natural killer cells to recognize and kill them. This suggests that combining
      BRAF-targeted therapy with aldesleukin, which activates more of these white blood cells, can
      lead to an increase in the death of cancer cells.

      In this research study, the investigators are looking to see whether the combination of
      vemurafenib (a BRAF-inhibitor) combined with aldesleukin(an immunotherapy drug) work together
      to produce a better health outcome in people with metastatic melanoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed metastatic or unresectable melanoma with V600E mutation

          -  Measurable disease

          -  May have received prior immunotherapy (excluding interleukin 2)

          -  Life expectancy greater than 3 months

          -  Recovered from effects of previous surgery and/or traumatic injury

          -  Must agree to use effective contraception

        Exclusion Criteria:

          -  Pregnant or breastfeeding

          -  Psychological, familial or other conditions that could hamper compliance with protocol

          -  Receiving other study agents

          -  History of carcinomatous meningitis

          -  Known active brain metastases

          -  Have received a BRAF inhibitor

          -  Uncontrolled intercurrent illness

          -  HIV positive on antiretroviral therapy

          -  History of a different malignancy within past 5 years (except cervical cancer in situ
             or basal/squamous cell carcinoma of the skin)

          -  Active hepatitis B or C

          -  Have received allogenic bone marrow transplant or organ transplant