Trial Information

A Phase I/II, Phase III and Extended Phase III Study of 18F-Fluorodeoxyglucose (FluGlucoScan) in Patients With Cancer or Suspected Cancer

Background

Positron Emission Tomography (PET) is a specialised Nuclear Medicine procedure that uses
positron emitting radiolabeled tracer molecules to measure biological activity. The
commonest of these radiolabeled tracers is 18F-Fluorodeoxyglucose (18F-FDG), which is used
to determine abnormal glucose metabolism in tumours and other sites. It has general
applications in all areas where abnormal glucose metabolism may be present including
circumstances such as differentiating tumour from scar tissue, evaluating the presence of
tumour in the light of rising tumour markers and normal morphological imaging techniques and
assessing response to therapy where other techniques are deemed to be unhelpful.

The Cross Cancer Institute has recently been funded to establish a PET centre that will
establish a research programme to prove the effectiveness of PET scanning in the Canadian
health care environment and validate the data that have been developed in other
jurisdictions in specific oncologic indications.

Objectives

Primary Objectives - The objectives of the clinical trial are to (a) demonstrate the safety
of 18F-FDG synthesised from cyclotron produced radiofluoride in the Coincidence Technologies
automated synthesis unit (ASU) in the Edmonton PET Centre facility and (b) confirm the
diagnostic effectiveness of 18F-FDG in subjects with known or suspected oncologic disease
and to compare this with values published in the literature.

Secondary Objectives - The secondary objectives of the clinical trial are to confirm the
general utility and value of 18F-FDG imaging of abnormal glucose metabolism in oncologic
applications, particularly with respect to Canadian practice.

Study Design

The proposed clinical trial will be a combined Phase I/II, Phase III, extended Phase III
(Phase I/II,III,exIII), diagnostic imaging, controlled, open label, single site, clinical
trial in a broad cross-section of CCI patients, including patients with Hodgkin and
non-Hodgkin lymphoma, colorectal cancer, breast cancer, melanoma, head and neck cancers,
PRUNK, esophageal cancer, thyroid cancer, NSCLC, SCLC, neuroendocrine tumours, and patients
with CNS tumours where conventional imaging methods have failed to yield a diagnostic
answer.

Each patient will usually receive a single IV injection of 18F-FDG. Imaging will be
conducted 30 to 60 minutes after an average injection of 200 - 300 MBq of 18F-FDG in
hydrated, fasted patients. Images will be collected for 40 to 60 minutes in 5 - 7 body
positions (total counts 5 to 15 million). For the Phase I/II study, images will be
interpreted by a single experienced Nuclear Medicine physician with regard to normal
physiological uptake of 18F-FDG. For the Phase III study, images will be interpreted
independently by two experienced Nuclear Medicine physicians with regard to normal
physiological uptake of 18F-FDG. The location and intensity of abnormal 18F-FDG uptake will
be noted and correlated with clinical findings, surgical or biopsy results or with
conventional imaging techniques, as available. The image review will be supplemented with
access to clinical and conventional imaging data in the Phase I/II study. In the Phase III
study all images will be reviewed independently by one physician blinded to all clinical
data except the primary diagnosis and by one physician with access to all relevant clinical
information. In the extended Phase III protocol the images will be interpreted by a single
physician with access to relevant clinical information

Statistical Analyses

Sample Size

The Phase I/II stage will enroll 20 subjects without regard for tumour type. The Phase III
stage will enroll approximately 300 subjects and the extended Phase III stage will enroll
approximately 3000 subjects with the approximate distribution by tumour type as follows:

Tumour Type Phase III:Extended Phase III

- Brain 10:100

- Colorectal 33:330

- Breast 21:210

- Lung (NSCLC & SCLC) 130:1300

- Lymphoma (Hodgkin's and non-Hodgkin's) 22:220

- Head & Neck 16:160

- Neuroendocrine 10:100

- Thyroid 29:290

- Melanoma 15:150

- PRUNK 14:140

Within each cancer subgroup in the Phase III stage, where disease status confirmation is
available, the sensitivity (true positive outcomes/true positive outcomes + false negative
outcomes) and positive predictive value (true positive outcomes/true positive outcomes +
false positive outcomes) will be calculated on a per patient basis. The general criteria for
assessment of comparability is that the study group sensitivity percent and positive
predictive value percent values have a difference of not less than 15 percent from the
appropriately matched literature values. For subgroups with significant patient numbers
statistical analysis of comparability will be undertaken.

Criteria for Evaluability of Study Subject Data All subjects enrolled in the Phase I/II
stage of the trial will be evaluated for safety. All subjects enrolled in the Phase III and
extended Phase III study will be evaluated for safety and efficacy.

Study Population

Number of Subjects to be Studied Phase I/II stage: ~ 20 Phase III stage: ~ 300 Extended
Phase III stage: ~ 3000 Some variation in the patient numbers studied is anticipated in the
Phase III and extended Phase III depending on local conditions and timing.

Inclusion Criteria for Selection of Study Subjects

Patients will be included in the study if they meet all of the following general criteria.

1. Male or female.

2. Known or suspected primary or metastatic tumours.

3. Age greater than or equal to 15

4. If female of child-bearing potential, a reliable method of contraception must be
combined with a negative pregnancy test before entering the study (contraception must
be used for 1 month after the last administration of 18F-FDG). If male, a barrier
method of contraception should be used for up to 1 month after the last administration
of 18F-FDG.

5. Able and willing to follow instructions and comply with the protocol.

6. Provide written informed consent prior to participation in the study.

7. Karnofsky Performance Scale Score 60-100.

Exclusion Criteria

Patients will be excluded from the study if they meet any of the following criteria:

1. significant renal impairment (serum creatinine > 200 µmol/L).

2. Coagulopathy (prothrombin time [PT] or activated partial thromboplastin time [APTT]
>1.5 times control).

3. Significant Thrombocytopenia (platelet count < 75,000/mm3).

4. Granulocytopenia (absolute neutrophil count < 1,000/mm3).

5. Blood glucose level Significant liver function impairment (total bilirubin > 2.0 mg/dL;
AST or ALT > 3 times the upper limit of normal) or greater than 10.

6. Presence of a severe infection.

7. Having had surgery or radiotherapy within 10 days of the planned imaging study.

8. Nursing or pregnant females.

9. Age less than 15.