Colorectal NeoplasmsPhase 1/2NCT00145665
The Role of Fluorothymidine Positron Emission Tomography (FLT-PET) in Proliferation of Colorectal Liver Metastases
A Phase 1/2 study testing FLT-PET scan in people with Colorectal Neoplasms and Liver Neoplasms, run by Radboud University Medical Center at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasms, Liver Neoplasms
- What is being tested?
- FLT-PET scan
- Type of treatment
- Surgery or procedure
- How many people
- 80 participants
- Where
- 1 siteNetherlands
- Study dates
- Jan 2005to Dec 2012
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Pregnancy
- Recent chemotherapy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Role of 3-Deoxy-3[18]Fluorothymidine Positron Emission Tomography (FLT-PET) in Proliferation of Colorectal Liver Metastases
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.
Read the 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.
- Conditions
- Colorectal Neoplasms, Liver Neoplasms
- Being tested
- FLT-PET scan
- Keywords
- FLT-PET, colorectal liver metastases, proliferation, proliferation markers, recurrence
- Medical subject headings
- Colorectal Neoplasms, Liver Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FLT-PET scanProcedure or surgery
Also called [18F]-3'-fluoro-3'-deoxy-L-thymidine Positron emission tomography scan
PET scan using FLT
What is being measured
The primary outcome is the main question the study is designed to answer.
correlation FLT-uptake in colorectal liver metastases and the histologically determined proliferation
Secondary outcomes (1)
correlation FLT and recurrence rate
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2005 (estimated)
- Study startJan 2005
- Primary completionDec 2011 (estimated)
- Study completionDec 2012 (estimated)
Why it stopped: no accrual achieved
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Investigators
- Bastiaan Wiering, MD, Principal investigator, Radboud University Medical CenterTheo MJ Ruers, MD, PhD, Principal investigator, Radboud University Medical CenterWim JG Oyen, MD, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00145665
- Sponsor's protocol ID
- FLT-PET CRC-LM
- Status last verified
- Feb 2007
- First submitted
- 1 Sep 2005
- Last updated
- 5 Sep 2011
- Results posted
- No
Publications
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. doi: 10.1200/JCO.1997.15.3.938.
PubMed 9060531Hughes 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. doi: 10.1007/BF02552560.
PubMed 3366020Gibbs 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. doi: 10.1002/(sici)1097-0142(19980401)82:73.0.co;2-f.
PubMed 9529015Tullo A, D'Erchia AM, Honda K, Mitry RR, Kelly MD, Habib NA, Saccone C, Sbisa E. Characterization of p53 mutations in colorectal liver metastases and correlation with clinical parameters. Clin Cancer Res. 1999 Nov;5(11):3523-8.
PubMed 10589767Buck 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.
PubMed 12067968Buck 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.
PubMed 12960187Francis 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. doi: 10.1007/s00259-003-1187-0. Epub 2003 May 9.
PubMed 12739071Vesselle 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.
PubMed 12960196Rodgers 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. doi: 10.1007/s10350-004-6581-6.
PubMed 12682536
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of 3-Deoxy-3[18]Fluorothymidine Positron Emission Tomography (FLT-PET) in Proliferation of Colorectal Liver Metastases
- ClinicalTrials.gov ID
- NCT00145665
- Acronym / sponsor ID
- FLT-PET CRC-LM
- Conditions
- Colorectal Neoplasms, Liver Neoplasms
- Keywords
- FLT-PET, colorectal liver metastases, proliferation, proliferation markers, recurrence
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: no accrual achieved
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Jan 2005
- Primary completion
- Dec 2011 (estimated)
- Study completion
- Dec 2012 (estimated)
- First posted
- 5 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Double blind (investigator, outcomes assessor)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (2 listed)
- Pregnancy
- Recent chemotherapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FLT-PET scanAlso: [18F]-3'-fluoro-3'-deoxy-L-thymidine Positron emission tomography scanPET scan using FLT | Procedure or surgery | – |
Primary outcome
correlation FLT-uptake in colorectal liver metastases and the histologically determined proliferation
1 secondary outcome
correlation FLT and recurrence rate
Results and safety
The study was stopped early (reason given: no accrual achieved). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2011.
- Background: PubMed 9060531Fong 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. doi: 10.1200/JCO.1997.15.3.938.
- Background: PubMed 3366020Hughes 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. doi: 10.1007/BF02552560.
- Background: PubMed 9529015Gibbs 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. doi: 10.1002/(sici)1097-0142(19980401)82:73.0.co;2-f.
- Background: PubMed 10589767Tullo A, D'Erchia AM, Honda K, Mitry RR, Kelly MD, Habib NA, Saccone C, Sbisa E. Characterization of p53 mutations in colorectal liver metastases and correlation with clinical parameters. Clin Cancer Res. 1999 Nov;5(11):3523-8.
- Background: PubMed 12067968Buck 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.
- Background: PubMed 12960187Buck 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.
- Background: PubMed 12739071Francis 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. doi: 10.1007/s00259-003-1187-0. Epub 2003 May 9.
- Background: PubMed 12960196Vesselle 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.
- Background: PubMed 12682536Rodgers 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. doi: 10.1007/s10350-004-6581-6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bastiaan Wiering, MD principal investigator
Radboud University Medical Center
Theo MJ Ruers, MD, PhD principal investigator
Radboud University Medical Center
Wim JG Oyen, MD, PhD principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing FLT-PET scan in people with Colorectal Neoplasms and Liver Neoplasms, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Sep 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: no accrual achieved). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
correlation FLT-uptake in colorectal liver metastases and the histologically determined proliferation. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00145665, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2011.