Trial Information

Multi-Tracer PET (Positron Emission Tomography) Assessment of Response in Various Malignancies in Early Phase Therapeutic Clinical Trials

Positron emission tomography (PET) is a molecular imaging modality that can probe various
aspects of tumor biology using a variety of radio-labeled imaging agents also called
"tracers". Oncologic PET imaging has seen a dramatic rise in clinical utilization over the
past decade for cancer detection, staging, and evaluating residual or recurrent disease
following therapy. These clinical scans use the tracer [18F]fluoro-2-deoxy-D-glucose (FDG),
which accumulates in cells in proportion to glucose (GLUT) transporter and hexokinase
activity. FDG provides a measure of tissue glucose metabolism. Concurrent with this
clinical growth, a number of other PET tracers have received significant attention in
research for a variety of imaging targets. Of special interest are the tracers
3'-deoxy-3'-[18F]fluorothymidine (FLT) and [15O]water (H215O). The uptake,
retention/washout, and ultimate biodistribution of these tracers are each related to
different functional or molecular processes. As such, each can be used to probe a different
aspect of tumor biology: FLT directly assesses tumor proliferation and H2O quantifies tumor
perfusion.

This companion clinical study is designed to obtain pre-therapeutic imaging assessments
using positron emission tomography (PET) imaging in 100 evaluable patients (those patients
who had baseline and follow-up PET imaging) with various forms of malignancy and at
approximately 28 days (day 25 -32).

Overview of the PET Tracers FDG, FLT, and H2O The use of more specifically targeted imaging
agents, such as PET radiopharmaceuticals, has great potential for overcoming the limitations
of standard anatomic imaging in malignancy

Hypotheses to be Tested:

The driving hypothesis for the overall line of research is that multiple PET imaging
biomarkers can provide improved image-guided personalized care of patients with various
malignancies.undergoing early phase therapeutic studies at Huntsman Cancer Institute (HCI).
The term "personalized care" is used here to broadly include the prediction of tumor
behavior prior to the start of therapy, tumor surveillance, prognostication, and eventually
individualized assignment of patients to conventional, aggressive, or investigational
therapies early in their clinical courses. This pilot project will obtain initial data on
the value of these PET biomarkers for such image-guided personalized care.

Specific hypotheses to be tested include:

- HYPOTHESIS I: Dynamic single-scan PET imaging provides biologically relevant
functional assessments of effect early in the course of therapy when compared to
standard Response Evaluation Criteria In Solid Tumors (RECIST)metrics of response. A
composite standardized uptake value (SUV) will be constructed from all the PET tracers
applied to each individual. Subjects with <35% decrease in composite SUV with be
classified as "progressing by PET", and subjects with ≥ 35% decrease in composite SUV
will be classified as "non-progressing by PET".

- HYPOTHESIS II: Multi-tracer PET biomarkers, obtained in conjunction with a novel
therapeutic, are better able to predict tumor aggressiveness than conventional
radiographic imaging. This will include better prediction of time to progression (TTP)
and patient survival

- HYPOTHESIS III: Characterization of multiple aspects of tumor function (glucose
metabolism, proliferation, and perfusion) at baseline and after therapy provides new
insight into tumor status that can eventually guide selection of the most appropriate
therapy.

Sufficient statistical power is expected to be obtained under this companion protocol to
validate the experimental imaging evaluations in hypothesis I. Hypotheses II and III will be
exploratory and provide insight into valuable information to be uses in subsequent
multi-tracer PET studies.

Data regarding these three hypotheses will be obtained in this work by studying the
correlation of PET imaging biomarkers with clinical outcomes and available tumor biologic
information.

Clinical Rationale:

This companion clinical study is designed to obtain pre-therapeutic imaging assessments
using positron emission tomography (PET) imaging in 100 evaluable patients (those patients
who had baseline and followup PET imaging) with various forms on malignancy and at
approximately 28 days (day 25-32), after institution of the therapeutic drug various primary
therapeutic clinical trials. The proposed PET imaging companion studies will be used in
various early phase clinical trials. The therapeutic trials will vary and the appropriate
companion PET imaging studies will be used to assess the most relevant therapeutic effect.
For example the table below delineates the therapeutic drug effect and which combination of
PET imaging agents would be most appropriate to assess early response at approximately 28
days (day 25-32).