CancerEarly Phase 1NCT02469129
PET Imaging of PARP Activity in Cancer
A Early Phase 1 study testing [18F]FluorThanatrace in people with Cancer, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The purpose of this research study is to determine the feasibility of using positron emission tomography (PET) imaging technology to image cancer with [18F]FluorThanatrace ([18F]FTT), a new radioactive tracer compound that has been developed that images poly(ADP-ribose) polymerase 1 (PARP-1) activity. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cancer
- What is being tested?
- [18F]FluorThanatrace
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2015to Jul 2025
- Phase
- Early Phase 1
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men or women 18 years of age or older.
- Healthy volunteers without history of cardiopulmonary conditions requiring any treatment or medical intervention and who are not current smokers (Dosimetry Studies Arm only).
- Patients with biopsy-proven diagnosis of head and neck squamous cell cancer (HNSCC) or any histopathologic type of lung cancer or any other type of cancer that can be treated with platinum-based chemotherapy as first-line therapy (which includes but is not limited to ovarian, gastric, and pancreatic cancers).
- At least one tumor site that is at least 1 cm in the shortest transaxial diameter by computed tomography (CT) (Kinetic Studies Arm only; disease-free participants can be enrolled in the Dosimetry Studies Arm).
Who cannot join
- History of claustrophobia or other preventing condition that has previously or would interfere with completion of protocol specified imaging sessions.
- Inability to comprehend or unwillingness to follow instructions for the study procedures as called for by the protocol.
- Presence of an implanted device that is incompatible with CT scanning.
- Non-measurable disease (< 1 cm) by CT (Kinetic Studies Arm only; disease-free participants can be enrolled in the Dosimetry Studies Arm).
- Unable to lie in the PET/CT scanner for the time required for scanning, up to 1 hour and 15 min at a time and possibly with arms raised above the head for lung imaging.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Positron Emission Tomography (PET) Imaging of Poly(ADP-Ribose) Polymerase (PARP) Activity in Cancer
The purpose of this research study is to determine the feasibility of using positron emission tomography (PET) imaging technology to image cancer with [18F]FluorThanatrace ([18F]FTT), a new radioactive tracer compound that has been developed that images poly(ADP-ribose) polymerase 1 (PARP-1) activity.
Read the detailed description
Poly(ADP-ribose) polymerase 1 (PARP1) is a deoxyribonucleic acid (DNA) repair enzyme that enables normal cell survival as well as certain cancers. Pharmaceutical companies have invested heavily in PARP1 inhibitor development because these agents can effectively treat certain cancers as single agents, thus sparing those patients from chemotherapy toxicities. However, clinical trials testing PARP1 inhibitors have demonstrated mixed results due to the inability to measure the degree of PARP1 inhibition in tumors reliably. Accurately measuring tumoral PARP1 activity levels before and after PARP1 inhibitor treatment will: (1) enable identification of patients whose tumors exhibit PARP activity and are therefore good candidates for PARP inhibitor therapy, and (2) confirm that adequate doses of PARP1 inhibitors are being administered to patients, thus improving dose selection for further study in clinical trials. Thus, noninvasive approaches for measuring tumoral PARP1 activity would have commercialization potential in not only supporting development of PARP1 inhibitors but also after Food and Drug Administration (FDA) approval to assess clinical PARP1 inhibitor treatment responses.
Inflammation also contributes to a number of diseases involving the lungs and other organs. Increasing evidence suggests that PARP1 may also play a central role in modulating immune inflammatory responses. Thus, the data from this trial will also be used to develop this approach for studying lung inflammatory responses.
A new radiolabeled compound, [18F]FluorThanatrace ([18F]FTT), has been generated which can be used to measure PARP1 activity noninvasively and quantitatively using positron emission tomography (PET). Our data in cancer models show that the uptake of our compound is specific for PARP1 activity and correlates with biochemically determined PARP1 activity. Additional preliminary data also suggests that decreased [18F]FTT uptake predicts tumor response to PARP inhibition with olaparib, a PARP1 inhibitor currently being evaluated in clinical trials. Therefore, the investigators are conducting this Phase 0 trial to develop [18F]FTT for clinical use in cancer patients.
To date, no biomarkers have been developed beyond genetic testing for breast cancer 1 and 2 (BRCA1/2) mutations that can aid in patient selection for treatment with PARP inhibition. Moreover, no technologies are available to monitor the efficacy of PARP inhibition. Our technology provides both a biomarker for patient selection as well as a means of monitoring PARP activity during treatment.
- Conditions
- Cancer
- Being tested
- [18F]FluorThanatrace
- Keywords
- positron emission tomography (PET) imaging, poly(ADP-ribose) polymerase 1 (PARP1), [18F]FluorThanatrace ([18F]FTT), PARP1 inhibitors, cancer treatments
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F]FluorThanatraceDrug
Also called [18F]FTT
For the Dosimetry Studies, 10 mCi of [18F]FTT will be injected intravenously, and participants will be placed in the following groups to be imaged with PET at the specified time points: 0 minute group--image at 0 and 120 min. after tracer injection; 30 minute group--image at 30 and 150 min. after tracer injection; 60 minute group--image at 60 and 180 min. after tracer injection; and 90 minute group--image at 90 and 210 min. after tracer injection.
For the Kinetic Studies, 10 mCi of [18F]FTT will be injected intravenously, and a 60-minute dynamic PET scan will be obtained starting at the time of injection.
| Study group | Role | What they receive |
|---|---|---|
| Dosimetry Studies Arm | Experimental | Twelve participants with cancer and eight healthy volunteers will be recruited first to undergo whole-body PET/CT imaging to determine the whole body dosimetry of [18F]FluorThanatrace. Receives: Drug: [18F]FluorThanatrace |
| Kinetic Studies Arm | Experimental | An additional 30 participants with cancer will undergo a 1-hour dynamic scan upon injection of [18F]FluorThanatrace to determine the kinetics of the tracer in tumors to correlate with tissue-based markers of PARP activity and to obtain metabolite information to help determine the best quantification approach for the PET images. When possible these subjects will also undergo 18F-FDG imaging for comparison to tumor metabolism Receives: Drug: [18F]FluorThanatrace |
What is being measured
The primary outcome is the main question the study is designed to answer.
Whole body effective dose and doses to critical organs (in rems) of a 10 millicurie (mCi) injection of [18F]FTT
Measured: This outcome measure is assessed from the [18F]FTT PET scan performed at the 1-day study visit.
Secondary outcomes (4)
[18F]FTT maximum standard uptake value (SUV) in tumors
Measured: This is measured from the [18F]FTT PET scan performed at the 1-day study visit.
Distribution volume ratio (DVR) of [18F]FTT in tumors by Logan plot analysis
Measured: This is measured from the [18F]FTT PET scan performed at the 1-day study visit.
PARP enzyme activity
Measured: This is measured from the [18F]FTT PET scan performed at the 1-day study visit.
% positive poly(ADP)ribosylated (PAR) cells by immunohistochemistry
Measured: This is measured from the scheduled 1-day clinically-indicated biopsy or resection occurring closest to the 1-day PET scan visit for cancer patients in the Kinetic Arm.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2015 (estimated)
- Study startMar 2015
- Primary completionJul 2024 (estimated)
- Study completionJul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Early Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Farrokh L Dehdashti, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02469129
- Sponsor's protocol ID
- 201410102
- Status last verified
- Dec 2023
- First submitted
- 1 Jun 2015
- Last updated
- 12 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Positron Emission Tomography (PET) Imaging of Poly(ADP-Ribose) Polymerase (PARP) Activity in Cancer
- ClinicalTrials.gov ID
- NCT02469129
- Acronym / sponsor ID
- 201410102
- Conditions
- Cancer
- Keywords
- positron emission tomography (PET) imaging, poly(ADP-ribose) polymerase 1 (PARP1), [18F]FluorThanatrace ([18F]FTT), PARP1 inhibitors, cancer treatments
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Mar 2015 (actual)
- Primary completion
- Jul 2024 (estimated)
- Study completion
- Jul 2025 (estimated)
- First posted
- 11 Jun 2015 (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 purpose of this research study is to determine the feasibility of using positron emission tomography (PET) imaging technology to image cancer with [18F]FluorThanatrace ([18F]FTT), a new radioactive tracer compound that has been developed that images poly(ADP-ribose) polymerase 1 (PARP-1) activity.
Detailed description
Poly(ADP-ribose) polymerase 1 (PARP1) is a deoxyribonucleic acid (DNA) repair enzyme that enables normal cell survival as well as certain cancers. Pharmaceutical companies have invested heavily in PARP1 inhibitor development because these agents can effectively treat certain cancers as single agents, thus sparing those patients from chemotherapy toxicities. However, clinical trials testing PARP1 inhibitors have demonstrated mixed results due to the inability to measure the degree of PARP1 inhibition in tumors reliably. Accurately measuring tumoral PARP1 activity levels before and after PARP1 inhibitor treatment will: (1) enable identification of patients whose tumors exhibit PARP activity and are therefore good candidates for PARP inhibitor therapy, and (2) confirm that adequate doses of PARP1 inhibitors are being administered to patients, thus improving dose selection for further study in clinical trials. Thus, noninvasive approaches for measuring tumoral PARP1 activity would have commercialization potential in not only supporting development of PARP1 inhibitors but also after Food and Drug Administration (FDA) approval to assess clinical PARP1 inhibitor treatment responses.
Inflammation also contributes to a number of diseases involving the lungs and other organs. Increasing evidence suggests that PARP1 may also play a central role in modulating immune inflammatory responses. Thus, the data from this trial will also be used to develop this approach for studying lung inflammatory responses.
A new radiolabeled compound, [18F]FluorThanatrace ([18F]FTT), has been generated which can be used to measure PARP1 activity noninvasively and quantitatively using positron emission tomography (PET). Our data in cancer models show that the uptake of our compound is specific for PARP1 activity and correlates with biochemically determined PARP1 activity. Additional preliminary data also suggests that decreased [18F]FTT uptake predicts tumor response to PARP inhibition with olaparib, a PARP1 inhibitor currently being evaluated in clinical trials. Therefore, the investigators are conducting this Phase 0 trial to develop [18F]FTT for clinical use in cancer patients.
To date, no biomarkers have been developed beyond genetic testing for breast cancer 1 and 2 (BRCA1/2) mutations that can aid in patient selection for treatment with PARP inhibition. Moreover, no technologies are available to monitor the efficacy of PARP inhibition. Our technology provides both a biomarker for patient selection as well as a means of monitoring PARP activity during treatment.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dosimetry Studies Arm | Experimental | Drug: [18F]FluorThanatraceTwelve participants with cancer and eight healthy volunteers will be recruited first to undergo whole-body PET/CT imaging to determine the whole body dosimetry of [18F]FluorThanatrace. |
| Kinetic Studies Arm | Experimental | Drug: [18F]FluorThanatraceAn additional 30 participants with cancer will undergo a 1-hour dynamic scan upon injection of [18F]FluorThanatrace to determine the kinetics of the tracer in tumors to correlate with tissue-based markers of PARP activity and to obtain metabolite information to help determine the best quantification approach for the PET images. When possible these subjects will also undergo 18F-FDG imaging for comparison to tumor metabolism |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Men or women 18 years of age or older.
- Healthy volunteers without history of cardiopulmonary conditions requiring any treatment or medical intervention and who are not current smokers (Dosimetry Studies Arm only).
- Patients with biopsy-proven diagnosis of head and neck squamous cell cancer (HNSCC) or any histopathologic type of lung cancer or any other type of cancer that can be treated with platinum-based chemotherapy as first-line therapy (which includes but is not limited to ovarian, gastric, and pancreatic cancers).
- At least one tumor site that is at least 1 cm in the shortest transaxial diameter by computed tomography (CT) (Kinetic Studies Arm only; disease-free participants can be enrolled in the Dosimetry Studies Arm).
Key exclusion criteria (5 listed)
- History of claustrophobia or other preventing condition that has previously or would interfere with completion of protocol specified imaging sessions.
- Inability to comprehend or unwillingness to follow instructions for the study procedures as called for by the protocol.
- Presence of an implanted device that is incompatible with CT scanning.
- Non-measurable disease (< 1 cm) by CT (Kinetic Studies Arm only; disease-free participants can be enrolled in the Dosimetry Studies Arm).
- Unable to lie in the PET/CT scanner for the time required for scanning, up to 1 hour and 15 min at a time and possibly with arms raised above the head for lung imaging.
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 |
|---|---|---|
| [18F]FluorThanatraceAlso: [18F]FTTFor the Dosimetry Studies, 10 mCi of [18F]FTT will be injected intravenously, and participants will be placed in the following groups to be imaged with PET at the specified time points: 0 minute group--image at 0 and 120 min. after tracer injection; 30 minute group--image at 30 and 150 min. after tracer injection; 60 minute group--image at 60 and 180 min. after tracer injection; and 90 minute group--image at 90 and 210 min. after tracer injection. For the Kinetic Studies, 10 mCi of [18F]FTT will be injected intravenously, and a 60-minute dynamic PET scan will be obtained starting at the time of injection. | Drug | Dosimetry Studies Arm, Kinetic Studies Arm |
Primary outcome
Whole body effective dose and doses to critical organs (in rems) of a 10 millicurie (mCi) injection of [18F]FTT
Time frame: This outcome measure is assessed from the [18F]FTT PET scan performed at the 1-day study visit.
4 secondary outcomes
[18F]FTT maximum standard uptake value (SUV) in tumors
Time frame: This is measured from the [18F]FTT PET scan performed at the 1-day study visit.
Distribution volume ratio (DVR) of [18F]FTT in tumors by Logan plot analysis
Time frame: This is measured from the [18F]FTT PET scan performed at the 1-day study visit.
PARP enzyme activity
Time frame: This is measured from the [18F]FTT PET scan performed at the 1-day study visit.
% positive poly(ADP)ribosylated (PAR) cells by immunohistochemistry
Time frame: This is measured from the scheduled 1-day clinically-indicated biopsy or resection occurring closest to the 1-day PET scan visit for cancer patients in the Kinetic Arm.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2023.
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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.
Farrokh L Dehdashti, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing [18F]FluorThanatrace in people with Cancer, run by Washington University School of Medicine 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 4 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: status not confirmed, as of the sponsor's last update on 12 Dec 2023. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
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?
Whole body effective dose and doses to critical organs (in rems) of a 10 millicurie (mCi) injection of [18F]FTT (time frame: This outcome measure is assessed from the [18F]FTT PET scan performed at the 1-day study visit.). 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 12 Dec 2023.