| General information |
| Database: | DB00660 |
| Objective: | Brain metastases commonly develop in patients with melanoma and are a frequent cause of death of patients with this disease. Ipilimumab improves survival in patients with advanced melanoma. They aimed to investigate the safety and activity of this drug specifically in patients with brain metastases. |
| Authors: | Margolin K, et al |
| Title: | Ipilimumab in patients with melanoma and brain metastases: an openlabel, phase 2 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2012 |
| PMID: | 22456429 |
| Trial Design |
| Clinical Trial Id: | NCT00623766 |
| Agent: | ipilimumab
|
| Target: | Cytotoxic Tlymphocyte antigen 4 (CTLA4)
|
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced melanoma with brain metastases |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an openlabel, phase II trial |
| Key Patients Feature: | pts of advanced melanoma with brain metastases |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Patients in cohort A were neurologically asymptomatic and were not receiving corticosteroid treatment at study entry; those in cohort B were symptomatic and on a stable dose of corticosteroids. |
| Treatment Info: | Patients in cohort A were neurologically asymptomatic and were not receiving corticosteroid treatment at study entry; those in cohort B were symptomatic and on a stable dose of corticosteroids. Patients were to receive four doses of 10 mg/kg intravenous ipilimumab, one every 3 weeks. Individuals who were clinically stable at week 24 were eligible to receive 10 mg/kg intravenous ipilimumab every 12 weeks. |
| Primary End Point: | the proportion of patients with disease control |
| Secondary End Point: | NA |
| Patients Number: | 72 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | in cohort A: mWHO vs irRC 1.4 (1.2-2.6) vs 2.7 (1.6-3.7). In cohort B: mWHO vs irRC 1.2 (1.2-1.3) vs 1.3 (1.2-2.5) |
| Median OS A vs. C: | 7.0 months (95% CI 4.1-10.8) in cohort A and 3.7 months (1.6-7.3) in cohort B |
| Adverse Event(agent arm): | The most common grade 3 adverse events in cohort A were diarrhoea (six patients [12%]) and fatigue (six [12%]); in cohort B, were dehydration (two individuals [10%]), hyperglycaemia (two [10%]), and increased concentrations of serum aspartate aminotransferase (two [10%]). One patient in each cohort had grade 4 confusion.The most common grade 3 immunerelated adverse events were diarrhoea (six patients [12%]) and rash (one [2%]) in cohort A, and rash (one individual [5%]) and increased concentrations of serum aspartate aminotransferase (two [10%]) in cohort B. One patient in cohort A died of drugrelated complications of immunerelated colitis. |
| Conclusions: | Ipilimumab has activity in some patients with advanced melanoma and brain metastases, particularly when metastases are small and asymptomatic. The drug has no unexpected toxic effects in this population. |