124I-FIAU Imaging in EBV and KSHV Associated Cancers

Study Overview
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Brief Summary
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This research is being done to determine whether viral thymidine kinase (TK) expression in Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV) virus-associated tumors is sufficient to image.

Detailed Description
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EBV and KSHV are associated with a variety of malignancies including some lymphomas, carcinomas and other malignancies. We anticipate that viral TK expression will differ among tumor types and will be adjusted with standard chemotherapies and some investigational agents. This exploratory study is aimed in part at evaluating whether standard regimens or investigational regimens might bring about sufficient activation of the EBV-TK or KSHV-TK in tumors to be therapeutically useful if used in conjunction with FIAU as a radiopharmaceutical.

Official Title
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Study of Imaging of Viral Thymidine Kinase Activity in EBV-Associated and KSHV-Associated Malignancies

Conditions
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Hodgkin Lymphoma, Non Hodgkin Lymphoma, Kaposi's Sarcoma, Gastric Cancer, Nasopharyngeal Cancer

Intervention / Treatment
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* Other: FIAU-PET-CT-2
* Other: FIAU-PET-CT-4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older. EBV-positive or KSHV-associated malignancy, including but not limited to: EBV+ Hodgkin lymphoma EBV+ non-Hodgkin lymphoma or lymphoproliferative disease Primary effusion lymphoma Kaposi's sarcoma EBV+ gastric cancer EBV+ nasopharyngeal cancer Measurable disease (at least one lesion measuring > 2 cm in longest axis). ECOG performance status of 0, 1, or 2. Patients must be able to lie flat for at least 60 minutes and fit on PET-CT scanner. For post-therapy imaging with FIAU-PET, treatment with standard or investigational agents that can potentially activate herpesvirus TK, including but not limited to the following. Concurrent radiation therapy is permissible: Platinum compounds (for example, cisplatin, carboplatin) Anthracyclines (for example, doxorubicin or pegylated doxorubicin) Tubulin disrupting agents (for example, vincristine, vinblastine) Rituximab Gemcitabine Cytarabine Histone deacetylase inhibitors Bortezomib NOTE: Patients who would not receive bortezomib as part of their usual care may receive a one-time dose of bortezomib for the purpose of imaging with 124I-FIAU and FIAU-PET-CT. AST and ALT < 3 X upper limit of normal, unless attributed to tumor, obtained within 2 weeks prior to registration. Serum creatinine < 2.0 mg/dL, within 2 weeks prior to registration. In patients who will receive bortezomib for imaging purposes only: Total bilirubin < 1.5 X upper limit of normal, obtained within 2 weeks prior to registration. Platelet count > 70,000 / mm3 obtained within 2 weeks prior to registration. No pre-existing peripheral neuropathy greater than grade 1. Exclusion Criteria: End-stage liver disease unrelated to tumor. Known active or chronic hepatitis B or hepatitis C infection. History of iodine hypersensitivity. Chronic renal insufficiency requiring dialysis. Women who are pregnant or breast feeding. Foreseen inability to comply with study requirements.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 4 mCi of I-FIAU<br>GROUP B 1-3 days after any chemotherapy that may activate viral TK, 4 mCi of I-FIAU are administered, followed 2 - 4 hours later by FIAU-PET-CT-4. | Other: FIAU-PET-CT-4<br>* 1-3 days after any chemotherapy that may activate viral TK, 4 mCi, rather than 2 mCi, of I-FIAU are administered, followed 2 - 4 hours later by FIAU-PET-CT<br>* Other names: FIAU-PET-CT;|
| Active Comparator: 2 mCi of I-FIAU<br>GROUP A 1-3 days after any chemotherapy that may activate viral TK, 2 mCi of I-FIAU are administered, followed 2 - 4 hours later by FIAU-PET-CT-2. | Other: FIAU-PET-CT-2<br>* 1-3 days after chemotherapy, subject get I-FIAU 2 mCi, then have FIAU-PET-CT done 2 - 4 hours after I-FIAU<br>* Other names: FIAU-PET-CT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the potential for enzymatic targeting as evidenced by the ability to image 124I-FIAU tracer uptake in tumor at baseline and following chemotherapy or biologic therapy with agents that may induce viral TK activation. |  | Baseline, Days 1-3 post chemo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To describe changes in viral DNA in plasma as a function of chemotherapy and the association with imaging by FIAU-PET |  | Baseline, pre chemo, post chemo, day 8 post chemo | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EBV+ malignancies, KSHV+ malignancies, HIV-associated lymphomas, Hodgkin Lymphoma, nonHodgkin Lymphoma or, nonHodgkins Lymphoproliferative Disease, Primary Effusion Lymphoma, Kaposi's Sarcoma, Gastric Cancer, Nasopharyngeal Cancer