Ibrutinib in Treating Patients With Refractory Metastatic Cutaneous Melanoma

Metastatic Melanoma Clinical Trial

Official title: A Phase 2 Study of Ibrutinib (PCI-32765) in Refractory Distant Metastatic Cutaneous Melanoma: Correlation of Biomarkers With Response and Resistance

Status Active, not recruiting

Clinical Trial Summary

This phase II trial studies how well ibrutinib works in treating patients with stage IV melanoma of the skin that has not responded to previous treatment. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Estimate rate of objective response (OR: complete response [CR] + partial response [PR]) to ibrutinib administered as single agent in patients with immune checkpoint inhibitor-refractory, or immune checkpoint inhibitor ineligible and mitogen-activated protein kinase (MAPK) inhibitor-refractory (if B-Raf proto-oncogene, serine/threonine kinase [BRAF]V600-mutant) or MAPK inhibitor-intolerant distant metastatic cutaneous melanoma.

SECONDARY OBJECTIVES:

I. Estimate progression-free survival (PFS) rate at 6 months after initiation of ibrutinib in patients with immune checkpoint inhibitor-refractory or immune checkpoint ineligible and MAPK inhibitor-refractory (if BRAFV600-mutant) or MAPK inhibitor-intolerant distant metastatic cutaneous melanoma.

II. Estimate overall survival (OS) after initiation of ibrutinib in patients with immune checkpoint inhibitor-refractory or immune checkpoint ineligible and MAPK inhibitor-refractory (if BRAFV600-mutant) or MAPK inhibitor-intolerant distant metastatic cutaneous melanoma.

III. Explore the association of ITK protein expression with OR and PFS.

TERTIARY OBJECTIVES:

I. Explore association between other putative targets of ibrutinib (e.g. Tec, ErbB4, Hck, Yes, BTK) in melanoma cells, as assessed by 2-color immunofluorescence (IF) in representative tissue sections obtained from pretreatment archived formalin-fixed paraffin-embedded (FFPE) tumor blocks or FFPE blocks obtained from fresh tissue biopsy from enrolled patients, with overall response (OR) and PFS.

II. Explore ibrutinib-mediated effect(s) on immune cell subsets associated with immunomodulation by performing multiparameter flow cytometric analysis in peripheral blood mononuclear cell (PBMC) obtained prior to treatment, on day 29 (i.e., predose day 1 of cycle 2) following initiation of treatment with ibrutinib, and at the time of disease progression (3 time points).

III. Determine pharmacokinetics (PK) of ibrutinib following daily dosing at 840 mg on day 8 of cycle 1 (Css).

OUTLINE:

Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 2 years. ;

Related Conditions & MeSH terms

• Melanoma
• Metastatic Melanoma
• Recurrent Cutaneous Melanoma
• Skin Neoplasms
• Stage IV Cutaneous Melanoma AJCC v6 and v7

• NCT number: NCT02581930
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 17, 2016
• Completion date: March 5, 2025