Evaluation of Tumor Response to Ipilimumab in the Treatment of Melanoma With Brain Metastases
Condition: Melanoma
MeSH terms: Melanoma; Brain Neoplasms
Intervention: Ipilimumab; Corticosteroid: Betamethasone; Corticosteroid: Dexamethasone; Corticosteroid: Fludrocortisone; Corticosteroid: Hydrocortisone; Corticosteroid: Meprednisone; Corticosteroid: Methylprednisolone; Corticosteroid: Prednisolone; Corticosteroid: Prednisone; Corticosteroid: Triamcinolone
Intervention description: 10 mg/kg, administered as an intravenous infusion every 3 weeks during induction and every 12 weeks during maintenance; Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with betamethasone; Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with dexamethasone; Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with fludrocortisone; Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with hydrocortisone; Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with meprednisone; Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with methylprednisolone; Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with prednisolone; Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with prednisone; Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with triamcinolone
Intervention MeSH terms: Dexamethasone; Prednisone; Methylprednisolone; Prednisolone; Triamcinolone; Hydrocortisone; Betamethasone; Fludrocortisone; Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 99.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No

Summary:

      To assess the response of melanoma with brain metastases to ipilimumab treatment while
      maintaining acceptable tolerability.
    

Eligibility criteria:

        Key inclusion criteria

          -  Histologically confirmed malignant melanoma

          -  At least 1 measurable index brain metastasis >0.5 cm and no larger than 3 cm in
             diameter that had not been previously irradiated, and/or 2 measurable lesions >0.3 cm
             visible on contrast magnetic resonance

          -  Index brain lesion must have resolved consequences of prior therapy that could have
             confounded attribution of tumor response including edema and hemorrhage

          -  Participants in ipilimumab monotherapy arm (including the first 21 who were enrolled
             in Stage 1) were to be free of neurologic symptoms related to metastatic brain lesions
             and must not have required or received systemic corticosteroid therapy in the 10 days
             prior to beginning ipilimumab therapy

          -  Eastern Cooperative Oncology Group performance status of 0 or 1

          -  Required values for initial laboratory tests:

               -  White blood cell count ≥2000/μL

               -  Absolute neutrophil count ≥1000/μL

               -  Platelets ≥100*10^3/μL

               -  Hemoglobin level ≥9 g/dL (may have been transfused)

               -  Aspartate aminotransferase/alanine aminotransferase (AST/ALT) level ≤2.5*ULN for
                  participants without liver metastasis

               -  AST/ALT level ≤5*ULN for those with liver metastasis

               -  Bilirubin level ≤2*ULN (except participants with Gilbert's Syndrome, who must
                  have had a total bilirubin level less than 3.0 mg/dL)

          -  Age 16 years and older

          -  Males and females

          -  Women of childbearing potential (WOBP) must be using an adequate method of
             contraception to avoid pregnancy throughout the study (and for up to 26 weeks after
             the last dose of investigational product) in such a manner that the risk of pregnancy
             is minimized. WOCBP include any female who has experienced menarche and who has not
             undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation,
             or bilateral oophorectomy) or is not postmenopausal.

        Key exclusion criteria

          -  History of carcinomatous meningitis, with prior stereotactic or highly conformal
             radiotherapy and/or whole brain irradiation within 14 days before the first dose of
             ipilimumab, and documented history of autoimmune disease

          -  Prior stereotactic or highly conformal radiotherapy and/or whole brain irradiation
             within 14 days prior to start of ipilimumab dosing for this study. Note the
             stereotactic radiotherapy field must not have included the brain index lesion or the
             lesion must have been detected and confirmed to be active and progressing after
             receiving whole brain irradiation.