Ipilimumab Induction in Patients With Melanoma Brain Metastases Receiving Stereotactic Radiosurgery
Condition: Metastatic Melanoma; Brain Metastases
MeSH terms: Melanoma; Neoplasm Metastasis; Brain Neoplasms
Intervention: Ipilimumab; Stereotactic Radiosurgery
Intervention description: Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses.; Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.
Intervention MeSH terms: Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic melanoma; Brain metastases; Radiation therapy; Immune therapy

Summary:

      This is a study to test the efficacy of using standard immune therapy for melanoma prior to
      stereotactic radiosurgery (ipilimumab induction), as compared to stereotactic radiosurgery
      followed by immune therapy. The study's hypothesis is that ipilimumab induction is as good as
      or better than controlling brain metastases as compared to stereotactic radiosurgery followed
      by immune therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with a histologically-confirmed diagnosis of melanoma who have imaging
             findings suggestive of 1 to 4 brain metastases

          -  At least one lesion in the brain that is measurable, which is defined as ≥5 x 5mm
             (Prior craniotomy and surgical resection is allowed, as long as there is at least one
             remaining measurable lesion in the brain)

          -  Patients must be candidates for stereotactic radiosurgery (SRS) and planning to
             undergo SRS

          -  Patients must be candidates for ipilimumab as determined by the treating physician

          -  Patients must be neurologically asymptomatic, or very minimally symptomatic, as judged
             by the treating physicians

          -  At least 3 weeks has elapsed from any prior therapy, and the patient has recovered
             from side effects to ≤ grade 1 toxicities per Common Terminology Criteria (CTC) for
             Adverse Events

          -  Age > or = 18 years old

          -  Performance status of ECOG of 0 or 1 (ECOG is the Eastern Oncology Cooperative Group
             Scoring system used to quantify cancer patients' general well-being and activities of
             daily life; scores range from 0 to 5 where 0 is perfect health and 5 is death)

          -  Adequate organ and marrow function: alanine aminotransferase (ALT ) < 2.5x's upper
             limit of normal (ULN) of the institutional normal reference range, aspartate
             aminotransferase (AST) < 2.5x's ULN of the institutional normal reference range,
             Bilirubin < 1.5x's ULN of the institutional normal reference range, Creatinine < 2.0
             milligrams per deciliter, Platelets > 50,000 per microliter

          -  Women of child-bearing potential must agree to use adequate contraception, defined as
             complete abstinence from intercourse with men or two methods

          -  Ability to understand and the willingness to sign a written informed consent

        Exclusion Criteria:

          -  Previous radiotherapy to the lesion(s) of interest, including prior treatment with
             whole brain radiation therapy (WBRT). Prior treatment with SRS is allowed if the index
             lesion(s) is in a different, non-contiguous location than the previously treated
             lesion.

          -  Patients who have previously received ipilimumab, PD-1 inhibitors or PD-L1 inhibitors
             are excluded due to the potential of effects on primary outcome

          -  Patients who require WBRT or surgery at the time of enrollment

          -  Neurologic symptoms or imaging findings that necessitate the use of steroids on the
             day of enrollment or in the prior 7 days

          -  Highly suspicious magnetic resonance imaging (MRI) or cerebrospinal fluid evidence of
             leptomeningeal metastases, unless all measurable disease is localized and SRS is
             considered the treatment of choice

          -  Concurrent treatment with any other anti-neoplastic drug or concurrent participation
             in another therapeutic clinical trial

          -  Patients unable to undergo or tolerate MRI scans (presence of cardiac pacemaker,
             implanted cardiac defibrillator, aneurysm clips, history of allergic
             reaction/hypersensitivity to gadolinium)

          -  Women who are pregnant or are nursing

          -  Patients with absolute lymphocyte count of <500 cells/microliter, who are known to be
             HIV positive, who have clinically significant active autoimmune disease, or are
             receiving immunosuppression following solid organ or stem cell transplant