EF5 in Melanoma Patients
| Status: | Completed |
|---|---|
| Conditions: | Skin Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 5/5/2014 |
| Start Date: | July 2012 |
| End Date: | September 2015 |
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
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.
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.
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
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