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

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 2

Conditions: Melanoma

Treatments: Drug: Corticosteroid: Prednisone; Drug: Corticosteroid: Fludrocortisone; Drug: Corticosteroid: Betamethasone; Drug: Corticosteroid: Dexamethasone; Drug: Ipilimumab; Drug: Corticosteroid: Hydrocortisone; Drug: Corticosteroid: Triamcinolone; Drug: Corticosteroid: Meprednisone; Drug: Corticosteroid: Methylprednisolone; Drug: Corticosteroid: Prednisolone

Study type: Interventional

Funder types: Industry

Identifiers

NCT00623766

CA184-042

Details and patient eligibility

About

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

Enrollment: 99 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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99 participants in 2 patient groups

Ipilimumab, 10 mg/kg, IV in corticosteroid-free patients

Experimental group

Description:

Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV, every 12 weeks, beginning at Week 24.

Treatment:

Drug: Ipilimumab

Ipilimumab, 10 mg/kg, IV in corticosteroid-dependent patients

Experimental group

Description:

Participants who were dependent on corticosteroid therapy received ipilimumab, 10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV, every 12 weeks, beginning at Week 24.

Treatment:

Drug: Corticosteroid: Prednisolone

Drug: Corticosteroid: Fludrocortisone

Drug: Ipilimumab

Drug: Corticosteroid: Prednisone

Drug: Corticosteroid: Hydrocortisone

Drug: Corticosteroid: Dexamethasone

Drug: Corticosteroid: Betamethasone

Drug: Corticosteroid: Methylprednisolone

Drug: Corticosteroid: Meprednisone

Drug: Corticosteroid: Triamcinolone