CancerPhase 1NCT00707343
[F-18] Fluorothymidine (FLT) Imaging on Patients With Primary Brain Tumors
A Phase 1 study testing FLT-PET Imaging in people with Cancer and Brain Tumors, run by University of Utah at 1 site in United States.
Trial summary
Despite significant advances in the understanding of brain tumor biology and genetics as well as improvements in surgical techniques, radiotherapy administration, and chemotherapy methods, many primary brain tumors remain incurable. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Brain Tumors
- What is being tested?
- FLT-PET Imaging
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Oct 2007to 30 Nov 2010
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Adult patients (n = 20) with primary brain tumors will be studied.
- All patients will have had previous radiation and may or may not have had chemotherapy for treatment of the primary brain tumor.
- All patients must have either radiological or established histological diagnosis of the following general categories: glioma (grade 2 to grade 4) previously treated with radiation therapy and possibly chemotherapy. It is expected that some of the patients may need a biopsy or neurosurgical procedure for diagnostic and/or therapeutic purposes as necessary treatment of their disease. In those instances the pathologic results will be used for correlation with the imaging findings. Only clinically indicated biopsy and/or surgery will be done and surgery is incidental to inclusion in the protocol.
- Patients must be 18 years or older for inclusion in this study.
- After entry into the study, the initial 12 patients are expected to be followed for at least 1 month after the infusion of [F-18]FLT.
- The patient, if female, must be postmenopausal for a minimum of one year or surgically sterile, or on one of the following methods of birth control for a minimum of one month prior to entry into this study: IUD, oral contraceptives, Depo-Provera or Norplant. These criteria can be waived at the discretion of the investigator if the patient's intracranial tumor is considered life threatening and the one month wait required is not in the best interest of the patient. Negative pregnancy test is accepted.
- Pre-treatment laboratory tests for patients receiving [F-18]FLT must be performed within 14 days prior to study entry. These must no greater or less than 4X the normal upper or lower limits. These will include liver enzymes (SGOT, SGPT, ALK Phos, GGT, LDH), bilirubin (direct and total), amylase, serum electrolytes, CBC with platelets and absolute neutrophil counts, prothrombin time, partial thromboplastin time, BUN, creatinine, and urinalysis.
- Pre-treatment radiological scans/studies (Gd- enhanced MRI and FDG-PET) for patients receiving [F-18]FLT must be performed within 10 days of study entry.
Who cannot join
- Patients with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness, are not eligible.
- Patients with known allergic or hypersensitivity reactions to previously administered radiopharmaceuticals. Patients with significant drug or other allergies or autoimmune diseases may be enrolled at the Investigator's discretion.
- Patients who are pregnant or lactating or who suspect they might be pregnant.
- Adult patients who require monitored anesthesia for PET scanning.
- HIV positive patients due to the previous toxicity noted with FLT in this patient group.
Trial locations and contacts
1 site in 1 country.
United States1 site
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
Official title: Preliminary Evaluation of the Efficacy of [F-18] Fluorothymidine (FLT) to Differentiate Radiation Necrosis From Tumor Recurrence and as a Marker of Proliferation in Patients With Primary Brain Tumors
Despite significant advances in the understanding of brain tumor biology and genetics as well as improvements in surgical techniques, radiotherapy administration, and chemotherapy methods, many primary brain tumors remain incurable. Most primary brain tumors are highly infiltrative neoplasms, and are therefore unlikely to be cured by local treatments such as surgery, focal radiotherapy, radiosurgery or brachytherapy. A particularly problematic aspect of the management of patients with brain tumors is the eventual development of enhancing lesions on MRI after radiation therapy. The treating physician is then left with the dilemma of what this enhancing lesion may represent (radiation necrosis versus recurrent tumor). The differential diagnosis is between recurrent tumor or radiation necrosis however the amount of each contributing to the enhancing mass on MRI is difficult if not impossible to assess. This particular problem is very common and most patients develop some degree of radiation necrosis after therapy with radiation. Differentiation of necrosis from recurrence is particularly challenging. MRI is typically unable to make this important distinction as there is simply an enhancing mass, the etiology of which could be either necrosis or recurrence. Other imaging methods such as FDG-PET have been used but this technique is also complicated in that the normal brain has FDG uptake and it is often difficult to differentiate recurrence from necrosis. [F-18]FLT may prove to be the most reliable method in making this important differentiation (necrosis versus recurrence) as normal brain and necrotic brain do not have proliferative activity and thus no [F-18]FLT uptake whereas tumor will have proliferative activity and thus [F-18]FLT uptake.
Read the detailed description
The primary objective of this study is to assess the preliminary efficacy of the radiopharmaceutical 3'-deoxy-3'-[F-18]fluorothymidine, [F-18]FLT, a radiopharmaceutical that directly assess tumor proliferation using Positron Emission Tomography (PET) in differentiating tumor recurrence from radiation necrosis in a group of 30 patients with glial neoplasms. This preliminary clinical study will investigate [F-18]FLT in patients with previously treated primary malignant brain tumors (WHO Grade II, III or IV glial-based tumors) who have a new or enlarging enhancing lesion on Gd-MRI and in whom it is not possible to differentiate recurrent tumor from radiation necrosis on the basis of conventional imaging techniques. The ability to make this important differentiation and accurately determine the amount/degree of tumor recurrence from the amount/degree of radiation necrosis in the enhancing mass is critical for the care of treated brain tumor patients and could potentially change patient management once validated as an accurate means of differentiating the amount/degree of radiation necrosis from recurrence.
While the safety of [F-18]FLT has been studied in a many patients to date we will also obtain additional safety data on the use of this agent in patients with primary brain tumors in a cohort of the initial 12 patients to be studied. It is important to emphasize that the potential clinical application of [F-18]FLT imaging in brain tumors must be compared to the current widely used imaging techniques of MRI and PET imaging using the agent, [F-18] fluorodeoxyglucose (FDG).
In this study, [F-18]FLT PET will be used to assess the three goals of this project:
- Show that imaging with [F-18]FLT and PET will or will not better determine the amount/degree of tumor versus necrosis in the abnormal areas seen on the recent MRI scan and FDG-PET scan.
- The [F-18]FLT radiopharmaceutical is shown to be safe or not safe in the amount administered in this study.
- The amount of [F-18]FLT that is seen on the PET study is shown to correlate or not to correlate with other tests used to determine the proliferation of brain tumors in a tissue sample of your newly identified abnormality on MRI in the event that another surgical biopsy or procedure is performed
- Conditions
- Cancer, Brain Tumors
- Being tested
- FLT-PET Imaging
- Medical subject headings
- Neoplasms, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FLT-PET ImagingRadiation
radiopharmaceutical 3'-deoxy-3'-[F-18]fluorothymidine, [F-18]FLT, a radiopharmaceutical that directly assess tumor proliferation using Positron Emission Tomography(PET) in differentiating tumor recurrence from radiation necrosis in a group of patients with glial neoplasms.
| Study group | Role | What they receive |
|---|---|---|
| All patients | Experimental | All participants enrolled. Receives: Radiation: FLT-PET Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Receiver Operating Curve (ROC AUC) Values for PET Imaging Techniques
The ROC AUC represents the probability that tumor recurrence will be differentiated from radiation necrosis.
Positron Emission Tomography (PET) imaging methods using radiopharmaceutical agents F-18 fluorodeoxyglucose (FDG) and F-18 fluorothymidine (FLT) were used for analysis. For F-18 FDG, the maximum standardized uptake value (SUVmax) with correction for body weight was measured at suspicious area of lesion enhancement. The ratio of F-18 FDG SUVmax of the suspicious lesion to that of the SUVmean of a 1 cm diameter region of normal contralateral white matter was also measured (F-18 FDG ratio lesion: contralateral white matter). For F-18 FLT, the maximum standardized uptake value (SUVmax) was measured at suspicious area of lesion enhancement. Patlak graphical analysis was applied using the metabolite-corrected plasma input function to obtain voxel-wise estimates of the FLT metabolic influx parameter (F-18 FLT Kimax).
Measured: 30 minutes for FDG imaging, 70 minutes for FLT imaging acquisition; 2-33 months for lesion outcome confirmation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2008 (estimated)
- Study start31 Oct 2007
- Primary completion30 Nov 2010
- Study completion30 Nov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by University of UtahThe 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
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John M Hoffman, MD, Principal investigator, Huntsman Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00707343
- Sponsor's protocol ID
- HCI20112
- Status last verified
- Sep 2021
- First submitted
- 26 Jun 2008
- Last updated
- 15 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preliminary Evaluation of the Efficacy of [F-18] Fluorothymidine (FLT) to Differentiate Radiation Necrosis From Tumor Recurrence and as a Marker of Proliferation in Patients With Primary Brain Tumors
- ClinicalTrials.gov ID
- NCT00707343
- Acronym / sponsor ID
- HCI20112
- Conditions
- Cancer, Brain Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- 31 Oct 2007 (actual)
- Primary completion
- 30 Nov 2010 (actual)
- Study completion
- 30 Nov 2010 (actual)
- First posted
- 30 Jun 2008 (estimated)
- Results
- Posted 3 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Despite significant advances in the understanding of brain tumor biology and genetics as well as improvements in surgical techniques, radiotherapy administration, and chemotherapy methods, many primary brain tumors remain incurable. Most primary brain tumors are highly infiltrative neoplasms, and are therefore unlikely to be cured by local treatments such as surgery, focal radiotherapy, radiosurgery or brachytherapy. A particularly problematic aspect of the management of patients with brain tumors is the eventual development of enhancing lesions on MRI after radiation therapy. The treating physician is then left with the dilemma of what this enhancing lesion may represent (radiation necrosis versus recurrent tumor). The differential diagnosis is between recurrent tumor or radiation necrosis however the amount of each contributing to the enhancing mass on MRI is difficult if not impossible to assess. This particular problem is very common and most patients develop some degree of radiation necrosis after therapy with radiation. Differentiation of necrosis from recurrence is particularly challenging. MRI is typically unable to make this important distinction as there is simply an enhancing mass, the etiology of which could be either necrosis or recurrence. Other imaging methods such as FDG-PET have been used but this technique is also complicated in that the normal brain has FDG uptake and it is often difficult to differentiate recurrence from necrosis. [F-18]FLT may prove to be the most reliable method in making this important differentiation (necrosis versus recurrence) as normal brain and necrotic brain do not have proliferative activity and thus no [F-18]FLT uptake whereas tumor will have proliferative activity and thus [F-18]FLT uptake.
Detailed description
The primary objective of this study is to assess the preliminary efficacy of the radiopharmaceutical 3'-deoxy-3'-[F-18]fluorothymidine, [F-18]FLT, a radiopharmaceutical that directly assess tumor proliferation using Positron Emission Tomography (PET) in differentiating tumor recurrence from radiation necrosis in a group of 30 patients with glial neoplasms. This preliminary clinical study will investigate [F-18]FLT in patients with previously treated primary malignant brain tumors (WHO Grade II, III or IV glial-based tumors) who have a new or enlarging enhancing lesion on Gd-MRI and in whom it is not possible to differentiate recurrent tumor from radiation necrosis on the basis of conventional imaging techniques. The ability to make this important differentiation and accurately determine the amount/degree of tumor recurrence from the amount/degree of radiation necrosis in the enhancing mass is critical for the care of treated brain tumor patients and could potentially change patient management once validated as an accurate means of differentiating the amount/degree of radiation necrosis from recurrence.
While the safety of [F-18]FLT has been studied in a many patients to date we will also obtain additional safety data on the use of this agent in patients with primary brain tumors in a cohort of the initial 12 patients to be studied. It is important to emphasize that the potential clinical application of [F-18]FLT imaging in brain tumors must be compared to the current widely used imaging techniques of MRI and PET imaging using the agent, [F-18] fluorodeoxyglucose (FDG).
In this study, [F-18]FLT PET will be used to assess the three goals of this project:
- Show that imaging with [F-18]FLT and PET will or will not better determine the amount/degree of tumor versus necrosis in the abnormal areas seen on the recent MRI scan and FDG-PET scan.
- The [F-18]FLT radiopharmaceutical is shown to be safe or not safe in the amount administered in this study.
- The amount of [F-18]FLT that is seen on the PET study is shown to correlate or not to correlate with other tests used to determine the proliferation of brain tumors in a tissue sample of your newly identified abnormality on MRI in the event that another surgical biopsy or procedure is performed
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All patients | Experimental | Radiation: FLT-PET ImagingAll participants enrolled. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Adult patients (n = 20) with primary brain tumors will be studied.
- All patients will have had previous radiation and may or may not have had chemotherapy for treatment of the primary brain tumor.
- All patients must have either radiological or established histological diagnosis of the following general categories: glioma (grade 2 to grade 4) previously treated with radiation therapy and possibly chemotherapy. It is expected that some of the patients may need a biopsy or neurosurgical procedure for diagnostic and/or therapeutic purposes as necessary treatment of their disease. In those instances the pathologic results will be used for correlation with the imaging findings. Only clinically indicated biopsy and/or surgery will be done and surgery is incidental to inclusion in the protocol.
- Patients must be 18 years or older for inclusion in this study.
- After entry into the study, the initial 12 patients are expected to be followed for at least 1 month after the infusion of [F-18]FLT.
Key exclusion criteria (5 listed)
- Patients with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness, are not eligible.
- Patients with known allergic or hypersensitivity reactions to previously administered radiopharmaceuticals. Patients with significant drug or other allergies or autoimmune diseases may be enrolled at the Investigator's discretion.
- Patients who are pregnant or lactating or who suspect they might be pregnant.
- Adult patients who require monitored anesthesia for PET scanning.
- HIV positive patients due to the previous toxicity noted with FLT in this patient group.
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 Imagingradiopharmaceutical 3'-deoxy-3'-[F-18]fluorothymidine, [F-18]FLT, a radiopharmaceutical that directly assess tumor proliferation using Positron Emission Tomography(PET) in differentiating tumor recurrence from radiation necrosis in a group of patients with glial neoplasms. | Radiation | All patients |
Primary outcome
Area Under the Receiver Operating Curve (ROC AUC) Values for PET Imaging Techniques
Time frame: 30 minutes for FDG imaging, 70 minutes for FLT imaging acquisition; 2-33 months for lesion outcome confirmation
The ROC AUC represents the probability that tumor recurrence will be differentiated from radiation necrosis. Positron Emission Tomography (PET) imaging methods using radiopharmaceutical agents F-18 fluorodeoxyglucose (FDG) and F-18 fluorothymidine (FLT) were used for analysis. For F-18 FDG, the maximum standardized uptake value (SUVmax) with correction for body weight was measured at suspicious area of lesion enhancement. The ratio of F-18 FDG SUVmax of the suspicious lesion to that of the SUVmean of a 1 cm diameter region of normal contralateral white matter was also measured (F-18 FDG ratio lesion: contralateral white matter). For F-18 FLT, the maximum standardized uptake value (SUVmax) was measured at suspicious area of lesion enhancement. Patlak graphical analysis was applied using the metabolite-corrected plasma input function to obtain voxel-wise estimates of the FLT metabolic influx parameter (F-18 FLT Kimax).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
John M Hoffman, MD principal investigator
Huntsman Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing FLT-PET Imaging in people with Cancer and Brain Tumors, run by University of Utah at 1 site in United States.
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 8 inclusion and 5 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: finished, as of the sponsor's last update on 15 Oct 2021. 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 United States. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Area Under the Receiver Operating Curve (ROC AUC) Values for PET Imaging Techniques (time frame: 30 minutes for FDG imaging, 70 minutes for FLT imaging acquisition; 2-33 months for lesion outcome confirmation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Oct 2021.