EF5 in Melanoma Patients

Phase 1

Completed

• Conditions: Melanoma
• Interventions: Drug: EF5 Hypoxia

• Registration Number: NCT01752257
• Lead Sponsor: Douglas Tyler

Brief Summary

The purpose of this pilot study is to determine the prevalence of markers of chronic and cycling hypoxia and reactive species stress (oxidative and nitrosative) in the melanoma tumor microenvironment. The study is based around four cornerstone features of the pathologic microenvironment - Hypoxia, Reactive Species (reactive oxygen and nitrogen species), HIF-1 and VEGF, which the investigators term the HRHV axis. Patients with in-transit melanoma (AJCC Stage IIIB or IIIC) (1) will be administered the hypoxia marker drug, EF5, 24 hr prior to isolated limb infusion (ILI) or hyperthermic isolated limb perfusion (HILP). Tumor biopsies will be performed just prior to ILI or HILP, at the 30 minute time point during ILI (or 60 minute time point during HILP), AND 24 hours after ILI or HILP. Tissues obtained will be snap frozen and subsequently analyzed for EF5 binding. Immunohistochemical analysis of a cohort of immunohistochemical and urine markers that depict the HRHV axis will also be examined. The association of the markers with the presence of hypoxia, as determined by EF5 positivity, will be determined. Data from this pilot study will be used to establish the prevalence of markers of the HRHV axis in melanoma. This information will be crucial for future human trials in which the HRHV axis is therapeutically targeted.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-07
• Study First Submitted: 2012-10-17
• Study First Submitted QC: 2012-12-14
• Study First Posted: 2012-12-19
• Primary Completion: 2014-08
• Study Completion: 2014-08
• Status Verified: 2015-03
• Last Update Submitted: 2015-03-06
• Last Update Posted: 2015-03-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
EF5 Hypoxia	EF5 Hypoxia	EF5 administered at 21mg/kg

Primary Outcome Measures

Name	Time	Method
Spatial comparison between marker proteins and hypoxia.	2 years	We will describe the distribution of the markers at each of the three time points with boxplots and means (with 80% confidence intervals). The variance of each marker will be partitioned into three parts: variance due to the time (i.e., treatment) effect, variance among patients, and error variance. This calculation can easily be done by fitting a general linear model in which marker is regressed on an n-1 degree of freedom patient effect (where n is the number of patients) and a 2 degree of freedom time effect. The error variance with 2\*(n-1) degrees of freedom is of course equal to the variance of the interaction of patient with time. Obviously, we would hope to find that the variance for the time effect is larger than either of the other two variances.

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States