EF5 in Measuring Tumor Hypoxia in Patients With Stage I-III Non-Small Cell Lung Cancer

Pilot Phase II Research Study of EF5 to Measure Tumor Hypoxia in Patients With Non-small Cell Lung Cancer

This pilot phase II trial studies how well EF5 works in measuring lack of tumor oxygen, hypoxia, in patients with stage I-III non-small cell lung cancer. EF5 may be effective in measuring the lack of oxygen in lung tumors and may allow doctors to plan better treatment.

Study Overview

• Status: Completed
• Conditions: Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IA Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: EF5; Procedure: Therapeutic Conventional Surgery; Other: Tissue Oxygen Measurement

Detailed Description

PRIMARY OBJECTIVES:

I. Assess the frequency and degree of hypoxia as measured by EF5 binding in patients with non-small cell lung cancer.

II. Correlate hypoxia as measured by EF5 binding with potential serum/plasma markers of hypoxia in patients with non-small cell lung cancer.

III. Correlate hypoxia as measured by EF5 binding with tissue markers of hypoxia in patients with non-small cell lung cancer.

IV. Correlate hypoxia as measured by EF5 binding with tumor angiogenesis in patients with non-small cell lung cancer.

V. Correlated hypoxia as measured by EF5 binding with apoptosis in patients with non-small cell lung cancer.

VI. Measure and characterize tumor perfusion in relationship to hypoxia in patients with non-small cell lung cancer.

VII. Correlate tumor perfusion to microvessel density in tumor samples in patients with non-small cell lung cancer.

VIII. Determine the longevity of EF5 adducts in human lung tumors.

OUTLINE:

Patients receive EF5 intravenously (IV) over 1-2.5 hours. Beginning 24-55 hours later, patients undergo tumor hypoxia measurement using a polarographic needle electrode and intraoperative tumor measurement before undergoing surgical biopsy or resection.

After completion of study treatment, patients are followed up for 4-6 weeks.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Durham, North Carolina, United States, 27705
      • Durham Veterans Affairs Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Known or suspected non-small cell lung cancer; patients without histologically or cytologically documented non-small cell lung cancer (NSCLC) must be estimated by their physician to have at least 75% probability of having NSCLC; the probability of malignancy will be predicted on the basis of known probabilities of individual clinical characteristics using a Bayesian model
• Clinical or pathologic stage I to III; patients in whom pre-surgical staging has not definitively establish stage IV disease are eligible
• Tumor mass at least 1.5 cm in maximum diameter must be present on computed tomography (CT) scan and must be included in the planned surgical biopsy or resection
• Patient must be planning to undergo a surgical staging or treatment procedure (including mediastinoscopy, wedge resection, lobectomy, or pneumonectomy) and have the clinical and physiological status appropriate for this procedure
• Performance status 0-2
• Bilirubin within normal limits
• Creatinine within normal limits or, if elevated, a creatinine clearance of at least 60 mL/min/m^2 (EF5 is primarily excreted via the kidney)
• White blood cell (WBC) > 2000/mm^3
• Platelets > 100,000/mm^3

Exclusion Criteria:

• Pregnancy or breast feeding; a negative serum pregnancy test is required of any woman of childbearing potential prior to enrollment; pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with EF5
• Allergy to IV contrast dye
• History of grade III or IV peripheral neuropathy as defined by the National Cancer Institute (NCI) Common Terminology Criteria (CTC)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (EF5); Patients receive EF5 IV over 1-2.5 hours. Beginning 24-55 hours later, patients undergo tumor hypoxia measurement using a polarographic needle electrode and intraoperative tumor measurement before undergoing surgical biopsy or resection.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: EF5; Given IV; Other Names: EF-5; Procedure: Therapeutic Conventional Surgery; Undergo surgery/thoracotomy; Other: Tissue Oxygen Measurement; Undergo tumor hypoxia measurement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and degree of hypoxia using a polarographic needle electrode		55 hours post-EF5 infusion
Serum/plasma markers of hypoxia	Spearman's rank correlation will be used to examine the relationship between hypoxia as measured by EF5 binding with serum markers of hypoxia (vascular endothelial growth factor [VEGF], D-Dimer, plasminogen activator inhibitor type 1 [PAI-1]).	55 hours post-EF5 infusion
Tissue markers of hypoxia	Spearman's rank correlation will be used to examine the relationship between hypoxia as measured by EF5 binding with tissue markers of hypoxia (hypoxia inducible factor 1 [HIF-1] alpha, involucrin).	55 hours post-EF5 infusion
Tumor perfusion using dynamic positron emission tomography	Spearman's rank correlation will be used to examine the relationship between hypoxia as measured by EF5 binding with tumor perfusion.	10 days prior to surgery

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Michael Kelley, Duke University

Study record dates

Study Major Dates

• Study Start: May 1, 2002
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: May 30, 2014
• First Submitted That Met QC Criteria: May 30, 2014
• First Posted (Estimate): June 3, 2014

Study Record Updates

• Last Update Posted (Estimate): April 13, 2015
• Last Update Submitted That Met QC Criteria: April 10, 2015
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Signs and Symptoms, Respiratory; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Hypoxia
• Other Study ID Numbers: NCI-2014-01169 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA014236 (U.S. NIH Grant/Contract); 2310 (CTEP); R21CA091565 (U.S. NIH Grant/Contract)