The Role of Fluorothymidine Positron Emission Tomography (FLT-PET) in Proliferation of Colorectal Liver Metastases

Colorectal Neoplasms Clinical Trial

Official title:

The Role of 3-Deoxy-3[18]Fluorothymidine Positron Emission Tomography (FLT-PET) in Proliferation of Colorectal Liver Metastases

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00145665
• Other study ID #: FLT-PET CRC-LM
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: September 1, 2005
• Last updated: September 2, 2011
• Start date: January 2005
• Est. completion date: December 2012

Study information

• Verified date: February 2007
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 80
• Est. completion date: December 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Investigator, Outcomes Assessor), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Liver Neoplasms
• Neoplasms

Intervention

Procedure:
• FLT-PET scan
PET scan using FLT

Locations

Country	Name	City	State
Netherlands	Radboud University	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

References & Publications (9)

Buck AK, Halter G, Schirrmeister H, Kotzerke J, Wurziger I, Glatting G, Mattfeldt T, Neumaier B, Reske SN, Hetzel M. Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG. J Nucl Med. 2003 Sep;44(9):1426-31. — View Citation

Buck AK, Schirrmeister H, Hetzel M, Von Der Heide M, Halter G, Glatting G, Mattfeldt T, Liewald F, Reske SN, Neumaier B. 3-deoxy-3-[(18)F]fluorothymidine-positron emission tomography for noninvasive assessment of proliferation in pulmonary nodules. Cancer Res. 2002 Jun 15;62(12):3331-4. — View Citation

Fong Y, Cohen AM, Fortner JG, Enker WE, Turnbull AD, Coit DG, Marrero AM, Prasad M, Blumgart LH, Brennan MF. Liver resection for colorectal metastases. J Clin Oncol. 1997 Mar;15(3):938-46. — View Citation

Francis DL, Visvikis D, Costa DC, Arulampalam TH, Townsend C, Luthra SK, Taylor I, Ell PJ. Potential impact of [18F]3'-deoxy-3'-fluorothymidine versus [18F]fluoro-2-deoxy-D-glucose in positron emission tomography for colorectal cancer. Eur J Nucl Med Mol Imaging. 2003 Jul;30(7):988-94. Epub 2003 May 9. — View Citation

Gibbs JF, Weber TK, Rodriguez-Bigas MA, Driscoll DL, Petrelli NJ. Intraoperative determinants of unresectability for patients with colorectal hepatic metastases. Cancer. 1998 Apr 1;82(7):1244-9. — View Citation

Hughes KS, Rosenstein RB, Songhorabodi S, Adson MA, Ilstrup DM, Fortner JG, Maclean BJ, Foster JH, Daly JM, Fitzherbert D, et al. Resection of the liver for colorectal carcinoma metastases. A multi-institutional study of long-term survivors. Dis Colon Rectum. 1988 Jan;31(1):1-4. — View Citation

Rodgers MS, Collinson R, Desai S, Stubbs RS, McCall JL. Risk of dissemination with biopsy of colorectal liver metastases. Dis Colon Rectum. 2003 Apr;46(4):454-8; discussion 458-9. — View Citation

Tullo A, D'Erchia AM, Honda K, Mitry RR, Kelly MD, Habib NA, Saccone C, Sbisà E. Characterization of p53 mutations in colorectal liver metastases and correlation with clinical parameters. Clin Cancer Res. 1999 Nov;5(11):3523-8. — View Citation

Vesselle H, Grierson J, Peterson LM, Muzi M, Mankoff DA, Krohn KA. 18F-Fluorothymidine radiation dosimetry in human PET imaging studies. J Nucl Med. 2003 Sep;44(9):1482-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	correlation FLT-uptake in colorectal liver metastases and the histologically determined proliferation
Secondary	correlation FLT and recurrence rate