Evaluation of Tumor Response to Ipilimumab in the Treatment of Melanoma With Brain Metastases

A Multi-Center Phase II Study to Evaluate Tumor Response to Ipilimumab (BMS-734016) Monotherapy in Subjects With Melanoma Brain Metastases

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

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.