Clinical trial NCT00145665: The Role of Fluorothymidine Positron Emission Tomography (FLT-PET) in Proliferation of Colorectal Liver Metastases
Official title: The Role of 3-Deoxy-3[18]Fluorothymidine Positron Emission Tomography (FLT-PET) in Proliferation of Colorectal Liver Metastases
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Colorectal Neoplasms
Liver Neoplasms
Keywords: FLT-PET
colorectal liver metastases
proliferation
proliferation markers
recurrence
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2005-09-05
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The aim of the study is to obtain information on FLT used in a PET-scan as a marker for the proliferation of colorectal liver metastases, so that the risk of recurrence can be identified in a noninvasive way, concerning patients with resectable colorectal liver metastases.

The hypothesis of this study is that a higher uptake of FLT in the liver metastases has a good correlation with the proliferation rate of the metastases. This rate is related to the risk of recurrence.

Detailed description: Aim of the Study:

Validation of FLT-PET as a proliferation marker for colorectal liver metastases, so that the risk of recurrence in patients with resected colorectal liver metastases can be assessed in a noninvasive method.

Study Design:

Validation study (n=40) to determine the correlation between quantitative FLT-PET (in this study determined before resection of the colorectal liver metastases) and the histologically determined proliferation index in the resected specimen of the metastases ('golden standard'). If correlation is established, the correlation between the proliferation and recurrence rate studied is also (n=80).

Study Population:

Patients with colorectal liver metastases.

Intervention:

FLT-PET scan

Scientific Basis of Study:

Several reports show that presence or absence of extrahepatic disease is a determining prognostic factor. Patients with extrahepatic disease are rarely suited for resection of the liver metastases. Recently several papers describe that the proliferation index of the liver metastases is another determining prognostic factor. Patients with a high proliferation factor have a worse prognosis. For both of these determining factors, it seems that PET diagnostics play an essential role and contribute to better selection of patients suitable for resection.

Diagnostics on Proliferation:

Seeing that the proliferation rate is preoperatively not determined without a biopsy (which is contraindicated due to dissemination), all patients with colorectal liver metastases (with no signs of extrahepatic deposits) are resected, without knowledge of the proliferation. FLT is a marker that visualizes proliferation and thus seems an ideal candidate to determine the proliferation rate in a noninvasive method. As of yet no validation studies of FLT-PET in colorectal liver metastases have been described.

Evaluation:

Quantitative histologic data are correlated with the quantitative FLT-PET data. If the correlation is higher that 0.85, this correlation is established. If this correlation is found, the inclusion of patients will be extended from 40 to 80 patients, seeing that this will give us the opportunity to correlate clinical data with the histological data. (alpha = 0.05, one-sided, beta = 0.90, assuming that an acceptable difference in sensitivity between both tests is 0 and an unacceptable difference is 0.02). If this correlation is significant, a new study will be proposed with the introduction of neoadjuvant chemotherapy, where the selection will be determined on basis of the proliferation rate.

Eligibility criteria: Inclusion Criteria:

* Colorectal liver metastases deemed resectable on three-phase computed tomography (CT)-scan of the liver
* No evidence of extrahepatic disease on CT chest and abdomen and possible fluorodeoxyglucose (FDG)-PET (if part of surgical work-up)
* No evidence of local recurrence or second primary colorectal tumor on colonoscopy or colonography
* Primary colorectal tumor radically removed
* Informed consent

Exclusion Criteria:

* Pregnancy
* Recent chemotherapy

Primary outcomes:
measure: correlation FLT-uptake in colorectal liver metastases and the histologically determined proliferation
Secondary outcomes:
measure: correlation FLT and recurrence rate
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center
name: Bastiaan Wiering, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Medical Center
name: Theo MJ Ruers, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Medical Center
name: Wim JG Oyen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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