124I-FIAU Imaging in EBV and KSHV Associated Cancers

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Completed

CT.gov ID

NCT00982449

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arms

Actual Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin Lymphoma Non Hodgkin Lymphoma Kaposi's Sarcoma Gastric Cancer Nasopharyngeal Cancer	Other: FIAU-PET-CT-2 Other: FIAU-PET-CT-4	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Dec 1, 2010

Actual Primary Completion Date :

Jul 1, 2013

Actual Study Completion Date :

Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 4 mCi of I-FIAU 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 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 Other Names: FIAU I-FIAU PET-CT FIAU-PET-CT
Active Comparator: 2 mCi of I-FIAU 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 1-3 days after chemotherapy, subject get I-FIAU 2 mCi, then have FIAU-PET-CT done 2 - 4 hours after I-FIAU Other Names: FIAU I-FIAU PET-CT FIAU-PET-CT

Arm

Intervention/Treatment

Active Comparator: 4 mCi of I-FIAU

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

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

Other Names:

FIAU

I-FIAU

PET-CT

FIAU-PET-CT

Active Comparator: 2 mCi of I-FIAU

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

1-3 days after chemotherapy, subject get I-FIAU 2 mCi, then have FIAU-PET-CT done 2 - 4 hours after I-FIAU

Other Names:

FIAU

I-FIAU

PET-CT

FIAU-PET-CT

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.