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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Stage IA Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

Treatments: Procedure: Therapeutic Conventional Surgery; Other: Laboratory Biomarker Analysis; Drug: EF5; Other: Tissue Oxygen Measurement

Study type: Interventional

Funder types: NIH

Identifiers

NCT02154399

2310 (Other Identifier)

R21CA091565 (U.S. NIH Grant/Contract)

NCI-2014-01169 (Registry Identifier)

P30CA014236 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 28 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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28 participants in 1 patient group

Treatment (EF5)

Experimental group

Description:

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.

Treatment:

Procedure: Therapeutic Conventional Surgery

Drug: EF5

Other: Laboratory Biomarker Analysis

Other: Tissue Oxygen Measurement