Imaging and Biomarkers of Hypoxia in Solid Tumors

Study Overview
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Brief Summary
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Hypoxia, meaning a lack of oxygen, has been associated strongly with a wide range of human cancers. Hypoxia occurs when tumor growth exceeds the ability of blood vessels to supply the tumor with oxygenated blood. It is currently understood that hypoxic tumors are more aggressive. Current methods for measuring hypoxia include invasive procedures such as tissue biopsy, or insertion of an electrode into the tumor. EF5-PET may be a non-invasive way to measure tumor hypoxia.

Detailed Description
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To establish PET imaging with the tracer EF5 as an accurate and reliable method for measuring the oxygen content of a tumor and to establish the measurement of secreted markers in blood as an accurate and reliable method for measuring the oxygen content of a tumor.

Official Title
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Imaging and Biomarkers of Hypoxia in Solid Tumors

Conditions
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Neoplasms

Intervention / Treatment
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* Procedure: PET Scan
* Drug: EF5
* Drug: Carbogen
* Drug: Dichloroacetate


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Any solid tumor malignancies of any stage meeting all of the following criteria: Minimum tumor dimension is at least 1 cm (to ensure it is above the detection threshold of PET imaging). Examples include but are not limited to: locally advanced squamous cell carcinoma of the head and neck to be treated by either initial surgery or primary chemoradiotherapy; inoperable non-small cell lung cancer or pancreatic carcinoma to be treated with stereotactic radiotherapy, which may be biopsied again at the time of percutaneous needle delivery of implanted fiducial markers. Patients with newly diagnosed malignancies should not have initiated treatment for their disease before participating in this study. Patients with recurrent or second malignancies may have had prior therapy as appropriate for their disease, but should have completed all prior treatment at least 30 days before participation in this study and should not have initiated new treatment for the current problem. Greater than or equal to eighteen years of age. Sufficiently healthy to tolerate all study procedures. Organ and marrow function sufficient to undergo planned therapy. Ability to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA • Pregnant or nursing

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carbogen arm<br> | Procedure: PET Scan<br>* radiation calculated per patient<br>* Other names: positron emission tomography;Drug: EF5<br>* 10 mCi, IV<br>* Other names: NSC-684681;Drug: Carbogen<br>* Calculated per patient<br>* Other names: Meduna's Mixture;|
| Experimental: DCA arm<br> | Procedure: PET Scan<br>* radiation calculated per patient<br>* Other names: positron emission tomography;Drug: EF5<br>* 10 mCi, IV<br>* Other names: NSC-684681;Drug: Dichloroacetate<br> <br> * Other names: DCA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 18F-EF5 uptake (tumor: blood ratio) before and after carbogen breathing for a subset of subjects. |  | 1-5 days | 
| 18F-EF5 uptake (tumor: blood ratio) before and after administration of DCA for a subset of subjects. |  | 1-5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of secreted hypoxia markers in plasma. |  | 1-5 days | 
| Hypoxia gene and protein expression scores in patients undergoing biopsy or surgical resection. |  | 1-5 days |