EF5 in Melanoma Patients

This study has been completed.
Sponsor:
Collaborator:
Varian Medical
Information provided by (Responsible Party):
Douglas Tyler, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01752257
First received: October 17, 2012
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Melanoma
Drug: EF5 Hypoxia
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
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

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Spatial comparison between marker proteins and hypoxia. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 15
Study Start Date: July 2012
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
EF5 Hypoxia
EF5 administered at 21mg/kg
Drug: EF5 Hypoxia
EF5 is a dye used to measure hypoxia

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01752257

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Douglas Tyler
Varian Medical
Investigators
Principal Investigator: Douglas Tyler, MD DUMC
  More Information

No publications provided

Responsible Party: Douglas Tyler, Chair, Surgical Oncology, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01752257     History of Changes
Other Study ID Numbers: Pro00033938
Study First Received: October 17, 2012
Last Updated: August 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
Melanoma

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas

ClinicalTrials.gov processed this record on October 21, 2014