Clinical Trial: Ibrutinib in Treating Patients With Refractory Stage IV Cutaneous Melanoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief 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.

Detailed Summary:

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 and mitogen-activated protein kinase (MAPK) inhibitor-refractory (if B-Raf proto-oncogene, serine/threonine kinase [BRAF]V600-mutant) distant metastatic cutaneous melanoma.

SECONDARY OBJECTIVES:

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

II. Estimate overall survival (OS) after initiation of ibrutinib in patients with immune checkpoint inhibitor-refractory and MAPK inhibitor-refractory (if BRAFV600-mutant) 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 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 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)
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Antitumor response, defined as the sum of complete response and partial response evaluated by RECIST criteria 1.1 [ Time Frame: Up to 1 year ]

Compute point estimate and 95% confidence interval for antitumor response.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • OS [ Time Frame: Duration of time from day 1 of treatment to death as a result of any cause, assessed up to 1 year ]
    Estimated using the Kaplan Meier method.
  • PFS [ Time Frame: Duration of time from day 1 of treatment to time of progression (based on clinical or radiographic grounds) or death as a result of any cause, whichever occurs first, assessed up to 1 year ]
    Estimated using the Kaplan Meier method.


Original Secondary Outcome: Same as current

Information By: National Cancer Institute (NCI)

Dates:
Date Received: October 20, 2015
Date Started: August 2016
Date Completion:
Last Updated: January 31, 2017
Last Verified: December 2016