Clinical Trial: Selumetinib in Treating Patients With Neurofibromatosis Type 1 and Dermal Neurofibroma

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Pilot Study of the MEK1/2 Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) for Adults With Neurofibromatosis Type 1(NF1) and Dermal Neurofibromas (DN)

Brief Summary: This pilot clinical trial studies how well selumetinib works in treating patients with neurofibromatosis type 1 and dermal neurofibromas. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine if selumetinib can result in shrinkage of dermal neurofibromas.

SECONDARY OBJECTIVES:

I. Assess the effect of selumetinib on the development on new dermal neurofibromas while on treatment with selumetinib.

II. Assess the effect of selumetinib on target inhibition in dermal neurofibroma(s) excised prior treatment and on treatment with selumetinib for analysis of percent inhibition of phosphorylated ERK (pERK), and changes in phosphorylated AKT (pAKT) and in the tumor kinome.

III. Assess the effect of selumetinib on the tumor microenvironment by analyzing peripheral blood bone marrow derived progenitor cells and cytokines obtained pretreatment and on treatment with selumetinib.

IV. Assess the effect of selumetinib skin related morbidity using the Skindex patient reported outcome measure.

V. Quantify the development of new dermal neurofibromas on treatment with selumetinib.

VI. Detailed pathologic analysis of dermal neurofibromas pretreatment and on treatment with selumetinib for changes in cell composition (including macrophage and mast cell infiltration).

OUTLINE:

Patients receive selumetinib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Change in the size of NF1 tumors and dermal neurofibromas assessed by digital photography [ Time Frame: Baseline to up to 1 year ]

The width, length, and height will be measured, and the volume of each of the neurofibromas measured will be calculated. The effect of selumetinib will be separately evaluated 3-5 small (longest neurofibroma diameter 3-7 mm) and 3-5 larger (longest neurofibroma diameter >= 8 mm) neurofibromas in each of the 3 regions. The sum of the on-treatment volumes for the smaller tumors will be subtracted from the pre-treatment volumes of the same tumors to arrive at an overall percentage change in tumor size for each patient. This will be repeated for the larger tumors. Then, the average percentage chan


Original Primary Outcome: Same as current

Current Secondary Outcome: Change in the number of neurofibromas [ Time Frame: Baseline to up to 1 year ]

Original Secondary Outcome: Same as current

Information By: National Cancer Institute (NCI)

Dates:
Date Received: July 20, 2016
Date Started: January 2017
Date Completion:
Last Updated: January 31, 2017
Last Verified: January 2017