An Imaging Study of [18]F-fluoro-3'-Deoxy-3'-L-fluorothymidine ([18]F-FLT) in Patients With Locally Advanced or Metastatic Pancreatic Cancer Who Will be Treated With Gemcitabine or Other Nucleoside Analogs

The objectives of this pilot study are: (i) to compare response to chemotherapy, time to disease progression and overall survival in patients with pancreatic cancer who will be treated with gemcitabine (or other nucleoside analogs) who demonstrate [18]F-FLT uptake to those patients who do not demonstrate [18]F-FLT uptake; (ii) to correlate [18]F-FLT uptake with hENT1 expression in biopsy samples where available; (iii)to determine the presence or absence of uptake, the relative uptake score (RUS), standardized uptake value (SUV), and tumor to background ratios (T/B) of [18]F-FLT in patients with known carcinoma of the pancreas and assess this uptake in relation to time to disease progression; and (iv) to demonstrate the safety of [18]F-FLT.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: [18]F-FLT PET scan

Detailed Description

The proposed clinical trial will be an imaging, open label, non-randomized, single site pilot study in patients with locally advanced or metastatic pancreatic carcinoma who will be treated with gemcitabine or other nucleoside analogs. Study participants will receive an IV injection of 2.59 MBq/kg ± 10% of [18]F-FLT (range: 100 to 350 MBq). If clinically indicated, dynamic PET scan imaging may start immediately before the injection, followed by half-body or limited frame scanning, using either a PET/CT or PET scanner. The first [18]F-FLT PET scan for each subject will occur within 4 weeks prior to commencement of his/her treatment. Study subjects will have a follow-up [18]F-FLT-PET scan at the time of disease progression, to a maximum of two [18]F-FLT PET scans. The same imaging procedure will be followed for both [18]F-FLT PET scans. At the same time as the [18]F-FLT PET scans occur, the patients' index tumour lesions will be re-evaluated by the same imaging modality originally used to assess the index lesions. Images will be interpreted by an experienced Nuclear Medicine physician with regard to normal physiological uptake of [18]F-FLT (RUS, SUV, and T/B). The location and relative uptake of normal and abnormal [18]F-FLT biodistribution patterns will be noted and correlated with time to disease progression and hENT1 expression in biopsy samples, where available. A medical chart review will be done at regular intervals to assess response to treatment, time to disease progression, and overall survival. Disease progression will be determined using the National Cancer Institute's Response Evaluation Criteria In Solid Tumours (RECIST).

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• male or female ≥ 18 years of age. If female of child bearing potential and outside of the window of 10 days since the first day of the last menstrual period, a negative pregnancy test
• patients with known locally advanced or metastatic carcinoma of the pancreas
• planned gemcitabine treatment
• calculated creatinine clearance >50ml/min (calculated by Crockcraft and Gault equation)
• able and willing to follow instructions and comply with the protocol
• provide written consent prior to participation in this study
• Karnofsky Performance Scale Score 60-100

Exclusion Criteria:

• Bilirubin ≥200 umol/L
• AST or ALT ≥5 times the upper limits of normal
• Serious medical conditions which may prevent a patient from tolerating experimental chemotherapy such as: congestive heart failure, unstable angina, unstable ventricular arrhythmia, uncontrolled psychiatric conditions, serious infections, uncontrolled diabetes
• uncontrolled brain metastasis. Patients who have stable brain metastasis treated with radiation or surgery who are symptomatic and a stable dose of dexamethasone are eligible
• nursing females

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [18]F-FLT PET scan; Radioactive dose of 2.59 MBq/kg (range 100 - 350 MBq) [18]F-FLT per injection prior to Positron Emission Tomography (PET) imaging. [18]F-FLT PET scans at baseline/pre-treatment and at disease progression, up to a maximum of two separate [18]F-FLT PET scans per participant.	Drug: [18]F-FLT PET scan; Injection of [18]F-FLT radiopharmaceutical followed by PET imaging.; Other Names: [18]F-FLT Positron Emission Tomography scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
compare response to chemotherapy, time to disease progression and overall survival in pancreatic cancer patients treated with gemcitabine who demonstrate 18F-FLT uptake to those patients who do not demonstrate 18F-FLT uptake	5 Years
correlate 18F-FLT uptake with hENT1 expression with biopsy samples where available	5 Years

Secondary Outcome Measures

Outcome Measure	Time Frame
determine the presence or absence of uptake, the relative uptake score (RUS) and tumor background ratios of 18F-FLT in patients with known carcinoma of the pancreas and assess this uptake in relation to time of disease progression	5 Years
to demonstrate the safety of 18F-FLT manufactured at the Edmonton PET Centre	5 Years

Collaborators and Investigators

• Sponsor: AHS Cancer Control Alberta
• Collaborators: Cross Cancer Institute
• Investigators: Principal Investigator: Michael B Sawyer, MD, Cross Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2007
• Primary Completion (Actual): February 6, 2019
• Study Completion (Actual): February 6, 2019

Study Registration Dates

• First Submitted: December 19, 2006
• First Submitted That Met QC Criteria: December 19, 2006
• First Posted (Estimate): December 21, 2006

Study Record Updates

• Last Update Posted (Actual): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 22, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Positron Emission Tomography (PET); 3'-deoxy-3'(18F)fluorothymidine ([18]F-FLT)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: DX-FLT-001