EF5 in Melanoma Patients

NCT ID: NCT01752257

Last Updated: 2015-03-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2014-08-31

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.

Conditions

Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

EF5 Hypoxia

EF5 administered at 21mg/kg

Group Type: OTHER

EF5 Hypoxia

Intervention Type: DRUG

EF5 is a dye used to measure hypoxia

Interventions

EF5 Hypoxia

EF5 is a dye used to measure hypoxia

Intervention Type: DRUG

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Varian, a Siemens Healthineers Company

INDUSTRY

Sponsor Role: collaborator

Douglas Tyler

OTHER

Sponsor Role: lead

Responsible Party

Douglas Tyler

Chair, Surgical Oncology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Douglas Tyler, MD

Role: PRINCIPAL_INVESTIGATOR

DUMC

Locations

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Other Identifiers

Pro00033938

Identifier Type: -

Identifier Source: org_study_id