NANT 2004-04: Phase I Study of Fenretinide (4-HPR, NSC 374551) Lym-X-Sorb? (LXS) Oral Powder in Patients with Recurrent or Resistant Neuroblastoma (IND #: 68,254)
NANT 2004-04
What is the goal of the study?
Fenretinide (N-(4-hydroxyphenyl)retinamide, 4-HPR), is a cytotoxic retinoid that has activity against neuroblastoma cell lines in vitro in a dose-related manner. Fenretinide has proven clinical tolerability at plasma doses of 1 - 18 ?M when given orally using a 100 mg capsule (NCI, IND#40294). However, the current 4-HPR oral capsule has low bioavailability, produces wide interpatient variability in peak and steady-state plasma levels, and is difficult to deliver in patients <4 years of age. thus 4-hpr pharmacokinetics and tumor response may benefit from an improved formulation of delivery. in an attempt to improve the antitumor activity of 4-hpr a novel oral 4-hpr powder formulation 4-hpr lxs oral powder 3 or 2.2 by weight 4-hpr has been prepared based on a lipid matrix technology called lym-x-sorb lxs. 4-hpr lxs oral powder is suitable for delivery in non-milk fat-containing foods specifically slim-fast liquid nutritional supplement. we hypothesize that 4-hpr lxs oral powder will: 1 allow drug administration to patients intolerant of the current nci 4-hpr capsule 2 produce more consistent and possibly higher 4-hpr plasma levels resulting in increased drug delivery to tumor cells and 3 facilitate the testing of fenretinide-based drug combinations. in the first phase of the current study modeled after the previous cog phase ii oral 4-hpr capsule study in recurrent resistant neuroblastoma anbl0321 patients receive 3 4-hpr lxs oral powder bid x 7 days every three weeks. primary study aims were to define the maximally tolerated dose mtd and toxicity profile of 4-hpr lxs oral powder and the pharmacokinetics of 4-hpr when given in 4-hpr lxs oral powder in pediatric patients with relapsed refractory neuroblastoma. secondary study aims were to assess the bioavailability of 4-hpr in 4-hpr lxs oral powder in peripheral blood mononuclear cells. levels of 4-hpr and its metabolites 4-mpr and 4-hpr were determined in peripheral blood mononuclear cells pbmc six hours after the am dose of 4-hpr lxs oral powder on day 6 of the second course. in the first phase of the study the dose was escalated to dose level 8 2210 mg 4-hpr m2 day without reaching a maximal tolerated dose.>
Who can participate in the study?
Please contact the study team listed below to learn more.