Clinical trial NCT01752257: EF5 in Melanoma Patients
Official title: Pilot Study to Characterize the HRHV Axis in the Microenvironment of Melanoma in Patients Undergoing Isolated Limb Infusion or Hypothermic Isolated Limb Perfusion With Melphalan
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma
Keywords: Melanoma
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Varian, a Siemens Healthineers Company
First posted: 2012-12-19
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: 3.1. Inclusion criteria

* Histologically confirmed AJCC Stage IIIB/IIIC/IV extremity melanoma who are undergoing ILI or HILP and have tumor available for biopsy (NOTE: patients with only 1 in-transit lesion are NOT eligible)
* Age ≥18
* KPS status ≥ 70
* Bilirubin ≤ 1.5x normal
* Creatinine ≤ 1.8 ( -EF5 is primarily excreted via the kidney)
* WBC \> 3000/mm3 and platelets \> 100,000/mm3

3.2. Exclusion criteria

* Pregnancy or breast feeding. A negative serum pregnancy test is required of any women childbearing potential prior to enrollment. Pregnant women are excluded from this study because EF5 is an agent with potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with EF5, breastfeeding should be discontinued if the mother is given EF5.
* Allergy to IV contrast dye
* History of grade III or IV peripheral neuropathy as defined by the NCI CTC (other 2-nitroimidazole compounds are neurotoxic)
* Previous history of any malignancy treated with radiotherapy and/or chemohormonal therapy

Primary outcomes:
measure: Spatial comparison between marker proteins and hypoxia.
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: DUMC
name: Douglas Tyler, MD
role: PRINCIPAL_INVESTIGATOR
References: