PARP Imaging with [18F]Florathanatrace for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Washington University School of Medicine

Disqualifiers: Claustrophobia, Implanted device, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses a special scan and a new radioactive substance to measure an enzyme's activity in cancer cells. It aims to help identify which cancer patients will benefit from specific treatments and ensure they get the right dose.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug [18F]FluorThanatrace for cancer?

The drug [18F]FluorThanatrace helps visualize how well PARP inhibitors, a type of cancer treatment, are working by showing the presence of a protein called PARP-1 in cancer cells. Studies have shown that it can effectively measure this protein in breast and ovarian cancer, helping doctors predict how well a patient might respond to PARP inhibitor therapy. ^{1 2 3 4 5}

Is [18F]FluorThanatrace safe for use in humans?

Initial studies involving [18F]FluorThanatrace, a PET radiotracer used to image a protein called PARP-1, have been conducted in humans, particularly in breast and ovarian cancer patients. These studies primarily focus on its ability to measure PARP-1 expression, but they do not report any specific safety concerns, suggesting it is generally safe for use in humans. ^{1 2 3 4 6}

How does the drug [18F]Florathanatrace differ from other cancer treatments?

[18F]Florathanatrace is unique because it is a PET radiotracer used for imaging PARP-1, a protein involved in DNA repair, which helps in visualizing and measuring PARP-1 expression levels in tumors. This imaging capability can aid in selecting patients for PARP inhibitor therapy and monitoring treatment effectiveness, unlike traditional treatments that do not offer this noninvasive visualization. ^{1 2 7 8 9}

Research Team

Farrokh Dehdashti, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults with a tumor at least 1 cm in size, or healthy volunteers without cardiopulmonary issues (for different study arms). It's open to those with certain cancers treatable by platinum-based chemo. People can't join if they can't follow the study plan, stay still in a PET/CT scanner, have incompatible implants, non-measurable disease under 1 cm, or conditions like claustrophobia that prevent imaging sessions.

Inclusion Criteria

I am 18 years old or older.

I have a tumor that is at least 1 cm wide, confirmed by a CT scan.

I am healthy, don't smoke, and have no heart or lung issues needing treatment.

Exclusion Criteria

Presence of an implanted device that is incompatible with CT scanning

I understand and am willing to follow the study's instructions.

You have a history of feeling very uncomfortable or anxious in small spaces, like an MRI machine, or any other condition that would make it difficult for you to complete required imaging sessions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dosimetry Studies

Participants undergo whole-body PET/CT imaging to determine the whole body dosimetry of [18F]FluorThanatrace

1 week

1 visit (in-person)

Kinetic Studies

Participants undergo a 1-hour dynamic scan upon injection of [18F]FluorThanatrace to determine the kinetics of the tracer in tumors

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging studies

4 weeks

Treatment Details

Interventions

• [18F]FluorThanatrace

Trial Overview [18F]FluorThanatrace ([18F]FTT), a new radioactive tracer for PET scans, is being tested to see if it can effectively image cancer activity related to an enzyme called PARP-1. The trial will assess how well this compound works for visualizing tumors in patients.

Participant Groups

Group I: Kinetic Studies Arm Experimental Treatment 1 Intervention

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

Group II: Dosimetry Studies Arm Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Findings from Research

The development of the PET radiotracer 18F-FTT for imaging PARP-1 has progressed from preclinical evaluation to first-in-human studies, showing promise as a biomarker for measuring PARP-1 levels in breast and ovarian cancer patients.

The article outlines the regulatory process for submitting an investigational new drug application to the FDA and emphasizes the need for a commercialization strategy to facilitate multicenter clinical trials for future approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Development of 18F Fluorthanatrace: A PET Radiotracer for Imaging Poly (ADP-Ribose) Polymerase-1. Lee, HS., Schwarz, SW., Schubert, EK., et al.[2023]

The study evaluated [18F]FluorThanatrace ([18F]FTT) as a biomarker to predict response to PARP inhibitors in homologous recombination deficient high-grade serous ovarian cancer, showing that a decrease in [18F]FTT uptake after treatment correlated with positive responses in patient-derived xenograft models and in 11 subjects.

In patients, a significant reduction in [18F]FTT uptake after about a week of PARP inhibitor treatment was associated with improved tumor response and progression-free survival, indicating that [18F]FTT could be a valuable tool for guiding PARP inhibitor therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]FluorThanatrace ([18F]FTT) PET Imaging of PARP-Inhibitor Drug-Target Engagement as a Biomarker of Response in Ovarian Cancer, a Pilot Study. Pantel, AR., Gitto, SB., Makvandi, M., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

In vivo visualization of PARP inhibitor pharmacodynamics. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

The Development of 18F Fluorthanatrace: A PET Radiotracer for Imaging Poly (ADP-Ribose) Polymerase-1. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

[18F]FluorThanatrace ([18F]FTT) PET Imaging of PARP-Inhibitor Drug-Target Engagement as a Biomarker of Response in Ovarian Cancer, a Pilot Study. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

PARP-1 Expression Quantified by [18F]FluorThanatrace: A Biomarker of Response to PARP Inhibition Adjuvant to Radiation Therapy. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Kinetic and Static Analysis of Poly-(Adenosine Diphosphate-Ribose) Polymerase-1-Targeted 18F-Fluorthanatrace PET Images of Ovarian Cancer. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

[(18)F]FluorThanatrace uptake as a marker of PARP1 expression and activity in breast cancer. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Dual-Modality Optical/PET Imaging of PARP1 in Glioblastoma. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Two experts and a newbie: [18F]PARPi vs [18F]FTT vs [18F]FPyPARP-a comparison of PARP imaging agents. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

An 18F-Labeled Poly(ADP-ribose) Polymerase Positron Emission Tomography Imaging Agent. [2019]