Phase II Randomized Trial of Ipilimumab Versus Ipilimumab and Radiotherapy in Metastatic Melanoma
Condition: Metastatic Melanoma
MeSH terms: Melanoma
Intervention: Ipilimumab; Radiation Therapy
Intervention description: Ipilimumab will be administered alone on day 4, 25, 46 and 67.; Radiation is given over one week interval On the fourth day of radiation (day 4)Ipilimumab is administered and repeated on Days 25, 46 and 67.
Intervention MeSH terms: Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 19 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Metastatic Melanoma; Radiation Therapy; Immunology; Abscopal

Summary:

      An attractive area of research regards immune manipulations to recover some of the patient's
      immune response to his/her tumor, a strategy that has the advantages of being both natural
      and potentially long-lasting.[1] We propose to combine immunotherapy with radiotherapy
      directed to a metastatic site, to create a "hub" for in vivo immunization to the tumor, to
      enable "tumor rejection" at the other metastatic sites. This "in vivo immunization" is
      explored as a viable alternative to an individualized vaccine approach. Preclinical data
      generated by us and others support a "proof of principle" clinical trial that may open the
      field to an alternative use of radiotherapy in a novel partnership with cancer
      immunotherapy.[2]
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ability to understand and the willingness to sign a written informed consent document;

          -  Histologic diagnosis of locally unresectable, metastatic melanoma.

          -  Any BRAF status is permitted

          -  Any prior therapy is permitted except prior therapy with ipilimumab.

          -  Patients must have at least 2 distinct measurable metastatic sites, with one of at
             least 1 cm or larger in its largest diameter and may have additional non-measurable
             but established metastatic lesions (i.e. bone metastases).

          -  Patients must have adequate organ and marrow function as defined by initial laboratory
             tests:

               -  WBC 2000/uL

               -  ANC 1000/uL

               -  Platelets 50 x 103/uL

               -  Hemoglobin 8 g/dL

               -  Creatinine 3.0 x ULN

               -  AST/ALT 2.5 x ULN for patients without liver metastasis

               -  Bilirubin 3.0 x ULN, (except patients with Gilbert's Syndrome, who must have a
                  total bilirubin less than 3.0 mg/dL;

          -  Performance status ECOG 0-1 or Karnofsky > 50%;

          -  Men and women, ages > 18 year old of age;

          -  Life expectancy > 3 months

          -  Stable brain metastases for at least 4 weeks and not steroid dependent;

          -  Women of childbearing potential (WOCBP) must be using an adequate method of
             contraception to avoid pregnancy throughout the study and for up to 8 weeks after the
             study.

        Exclusion Criteria:

          -  Patients having no lesions outside the field of radiation thus nullifying the ability
             to measure an abscopal effect;

          -  Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded
             from this study as are patients with a history of symptomatic disease (e.g.,
             rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus
             Erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis;

          -  Any underlying medical or psychiatric condition, which in the opinion of the
             Investigator, will make the administration of study drug hazardous or obscure the
             interpretation of AEs, such as a condition associated with frequent diarrhea;

          -  Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to
             one month prior to or after any dose of ipilimumab);

          -  Concomitant therapy with any of the following: IL-2, interferon or other non-study
             immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other
             investigation therapies; or chronic use of systemic corticosteroids;

          -  Women who are unwilling or unable to use an acceptable method to avoid pregnancy for
             the entire study period and for at least 8 weeks after cessation of study drug, or
             have a positive pregnancy test at baseline, or are pregnant or breastfeeding;

          -  Persons of reproductive potential must agree to use and utilize an adequate method of
             contraception throughout treatment and for at least 8 weeks after study drug is
             stopped;

          -  Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
             treatment of either a psychiatric or physical (e.g., infectious) illness.