Pilot Phase II Research Study of EF5 to Measure Tumor Hypoxia in Patients With Non-small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- EF5
- Conditions
- Stage IA Non-Small Cell Lung Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 28
- Locations
- 2
- Primary Endpoint
- Frequency and degree of hypoxia using a polarographic needle electrode
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
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.
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.
Investigators
Eligibility Criteria
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)
Arms & Interventions
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.
Intervention: EF5
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.
Intervention: Laboratory Biomarker Analysis
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.
Intervention: Therapeutic Conventional Surgery
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.
Intervention: Tissue Oxygen Measurement
Outcomes
Primary Outcomes
Frequency and degree of hypoxia using a polarographic needle electrode
Time Frame: 55 hours post-EF5 infusion
Serum/plasma markers of hypoxia
Time Frame: 55 hours post-EF5 infusion
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 \[PAI-1\]).
Tissue markers of hypoxia
Time Frame: 55 hours post-EF5 infusion
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).
Tumor perfusion using dynamic positron emission tomography
Time Frame: 10 days prior to surgery
Spearman's rank correlation will be used to examine the relationship between hypoxia as measured by EF5 binding with tumor perfusion.