PET Imaging for Breast Cancer

Overseen By Jennifer Specht, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Washington

Must be taking: PARP inhibitors

Disqualifiers: Myelodysplastic syndrome, Acute myeloid leukemia, others

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

Compensation: Varies

Number of Visits: 2

22 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial studies how well fluorine F 18 fluorthanatrace (\[18F\]FTT) positron emission tomography (PET) works in imaging patients with breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) who are receiving standard of care (SOC) poly (ADP-ribose) polymerase (PARP) inhibitors with or without immune checkpoint inhibitors (ICI) to be able to detect clinical response to PARP inhibitor ± ICI treatment. \[18F\]FTT is a radiotracer that targets and binds to PARP1 which can potentially be used for the imaging of PARP1 expression using PET. Once administered, \[18F\]FTT targets and binds to PARP1. Upon PET, PARP1-expressing tumor cells can be visualized. PET is an established imaging technique that utilizes small amounts of radioactivity attached to very minimal amounts of tracer, in the case, \[18F\]FTT. Because some cancers take up \[18F\]FTT it can be seen with PET. PARP inhibitors work as a targeted therapy by blocking an enzyme involved in repairing cell damage. It may cause tumor cells to die. ICI may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Combining \[18F\]FTT with a PET scan may help detect tumor cells better in patients with metastatic breast cancer who are receiving standard of care PARP inhibitors with our without ICI treatment.

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 to get a clear answer.

What data supports the effectiveness of the drug Immune Checkpoint Inhibitor, Poly (ADP-Ribose) Polymerase Inhibitor for breast cancer?

Research shows that Poly (ADP-Ribose) Polymerase inhibitors (PARPis) are effective in treating breast cancer, as they interfere with DNA replication in cancer cells. Additionally, a study using a PET imaging agent demonstrated that PARPis can significantly reduce the binding of a tracer in breast cancer, indicating effective drug-target engagement. ^{1 2 3 4 5}

Is PET imaging with PARP inhibitors safe for humans?

PARP inhibitors, used in breast cancer treatment, have been tested in clinical trials and are generally considered safe, but they can have different side effects depending on the specific drug and dosage. It's important to discuss potential risks with your healthcare provider. ^{3 6 7 8 9}

How is the drug Poly (ADP-Ribose) Polymerase Inhibitor unique for breast cancer treatment?

This drug is unique because it uses PET imaging to visualize and measure the drug's engagement with its target, PARP, in the body. This allows doctors to see how well the drug is working in real-time, which is not possible with most other treatments. ^{1 2 6 10 11}

Research Team

Jennifer Specht, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for patients with breast cancer that has spread to other body parts. Participants must be receiving standard PARP inhibitors, which are drugs targeting specific enzymes in cancer cells, and may also be getting immune checkpoint inhibitors as part of their usual care.

Inclusion Criteria

I am willing to have a biopsy if I undergo a specific PET scan during my treatment.

For women of childbearing potential, a negative serum pregnancy test is required within 7 days prior to [18F]FTT PET imaging on day 1. For women who obtain on-treatment (12-week) [18F]FTT imaging, a negative serum pregnancy test will be required within 7 days prior to [18F]FTT PET imaging

My breast cancer has spread to other parts of my body.

Exclusion Criteria

I have had myelodysplastic syndrome or acute myeloid leukemia.

Pregnant or breastfeeding women

I can swallow pills and do not have stomach issues affecting medication absorption.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Initial Imaging and Treatment Initiation

Participants receive [18F]FTT IV and undergo PET scan 60-75 minutes later on day 1 of initiating SOC PARP inhibitor ± ICI therapy

1 day

1 visit (in-person)

Follow-up Imaging

Participants undergo follow-up PET/CT scans at 12 weeks and 6 months, with potential tissue biopsies

6 months

Multiple visits (in-person)

Treatment Details

Interventions

• Immune Checkpoint Inhibitor
• Poly (ADP-Ribose) Polymerase Inhibitor

Trial Overview [18F]FTT PET scans are being tested to see if they can better detect tumor cells in metastatic breast cancer patients undergoing treatment with PARP inhibitors, alone or combined with immune checkpoint inhibitors. The scan uses a special dye that highlights active tumor cells on imaging.

Participant Groups

Group I: Arm I ([18F]FTT PET, FDG PET/CT, PARP inhibitor, ICI) Experimental Treatment 9 Interventions

Patients receive \[18F\]FTT IV and undergo PET scan 60-75 minutes later on day 1 of initiating SOC PARP inhibitor ± ICI therapy and again at 12 weeks. At least 1-7 days later, patients undergo SOC FDG PET/CT and follow up scans at 12 weeks and 6 months. Patients may also undergo tissue biopsy during screening and during follow up.

Group II: Arm II ([18F]FTT PET, FDG PET/CT, PARP inhibitor, ICI) Active Control 9 Interventions

Patients receive \[18F\]FTT IV and undergo PET scan 60-75 minutes later on day 1 of initiating SOC PARP inhibitor ± ICI therapy. At least 1-7 days later, patients undergo SOC FDG PET/CT and follow up scans at 12 weeks and 6 months. Patients may also undergo tissue biopsy during screening.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Breast Cancer Research Foundation

Collaborator

Trials

79

Recruited

40,500+

References

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

In vivo visualization of PARP inhibitor pharmacodynamics. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Preclinical and first-in-human-brain-cancer applications of [18F]poly (ADP-ribose) polymerase inhibitor PET/MR. [2022]

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

Where Do We Stand on the Integration of PARP Inhibitors for the Treatment of Breast Cancer? [2019]

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

A PET imaging agent for evaluating PARP-1 expression in ovarian cancer. [2023]

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

The evolving landscape of predictive biomarkers of response to PARP inhibitors. [2021]

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

[18F]-SuPAR: A Radiofluorinated Probe for Noninvasive Imaging of DNA Damage-Dependent Poly(ADP-ribose) Polymerase Activity. [2020]

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

PARP inhibitors in breast cancer. [2015]

8. Scotland pubmed.ncbi.nlm.nih.gov

PARP inhibitors in cancer therapy: two modes of attack on the cancer cell widening the clinical applications. [2016]

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

PARP Inhibitors for the Treatment and Prevention of Breast Cancer. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Synthesis, [¹⁸F] radiolabeling, and evaluation of poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors for in vivo imaging of PARP-1 using positron emission tomography. [2022]

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

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