PET Imaging of PARP Activity in Cancer

December 11, 2023 updated by: Washington University School of Medicine

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dosimetry Studies Arm
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.
Drug: [18F]FluorThanatrace

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.

Other Names:
  • [18F]FTT
Experimental: Kinetic Studies Arm
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
Drug: [18F]FluorThanatrace

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.

Other Names:
  • [18F]FTT

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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.
This outcome measure is assessed from the [18F]FTT PET scan performed at the 1-day study visit.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
[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.
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.
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.
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Washington University School of Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Farrokh L Dehdashti, MD, Washington University School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2015

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 1, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 8, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 11, 2015

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 12, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 11, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201410102

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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