[18F]FluorThanatrace PET/CT Imaging for Ovarian Cancer

Overseen By Fiona Simpkins, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Abramson Cancer Center of the University of Pennsylvania

Disqualifiers: Pregnancy, Breastfeeding, Imaging intolerance, others

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

Compensation: Varies

Number of Visits: 2

35 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

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.

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

The development of [18F]FluorThanatrace included first-in-human imaging studies, which are initial steps in assessing safety, but specific safety data for humans is not detailed in the available research. ^{1 2 3 4 5}

How is [18F]FluorThanatrace PET/CT imaging different from other treatments for ovarian cancer?

[18F]FluorThanatrace PET/CT imaging is unique because it uses a special radiotracer to noninvasively measure the expression of PARP-1, a protein targeted by certain ovarian cancer drugs. This imaging technique helps predict how well a patient might respond to PARP inhibitors, which are standard treatments for some types of ovarian cancer. ^{1 4 6 7 8}

What is the purpose of this trial?

Up to 40 evaluable women with known or suspected epithelial ovarian, fallopian tube, or primary peritoneal cancer will participate in two different imaging cohorts. The Biodistribution cohort will include up to 4 patients and the Dynamic cohort will include up to 36 patients. Human dosimetry will be calculated from the Biodistribution cohort. The Dynamic cohort date will evaluate preliminary information on uptake of \[18F\]FTT in gynecological cancer and compare with PARP-1 activity in tissue.

Research Team

Fiona Simpkins, MD

Principal Investigator

Abramson Cancer Center at Penn Medicine

Eligibility Criteria

This trial is for women aged 18 or older with known or suspected epithelial ovarian, fallopian tube, or primary peritoneal cancer. They must have at least one lesion that's visible on standard imaging and can be either newly diagnosed or have recurrent cancer. Pregnant or breastfeeding women and those unable to tolerate imaging procedures are excluded.

Inclusion Criteria

I have or had ovarian, fallopian tube, or peritoneal cancer.

At least one lesion ≥ 1.0 cm that is seen on standard imaging (e.g. CT, MRI, ultrasound, FDG PET/CT)

Exclusion Criteria

Inability to tolerate imaging procedures in the opinion of an investigator or treating physician

Females who are pregnant or breast feeding at the time of screening will not be eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential at screening.

My doctor thinks I have a health issue that could make participating in the study unsafe for me.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Biodistribution Imaging

Participants in the Biodistribution cohort undergo a series of vertex to mid-thigh biodistribution [18F]FTT PET/CT scans over approximately 4 hours

1 day

1 visit (in-person)

Dynamic Imaging

Participants in the Dynamic cohort undergo 1 static skull base to mid-thigh scan imaging post injection of [18F]FTT

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

Treatment Details

Interventions

• [18F]FluorThanatrace

Trial Overview [18F]FluorThanatrace (FTT) is being tested in this study using PET/CT scans to understand its distribution, metabolism, and excretion in patients with gynecological cancers. The trial has two parts: a Biodistribution cohort for dosimetry calculations and a Dynamic cohort to assess FTT uptake compared to PARP-1 activity in tissues.

Participant Groups

Group I: Dynamic Experimental Treatment 2 Interventions

The Dynamic cohort will include up to 36 patients who will undergo 1 static skull base to mid-thigh scans imaging post injection of \[18F\]FTT.

Group II: Biodistribution Experimental Treatment 2 Interventions

The Biodistribution cohort will include up to 4 patients who will undergo a series of vertex to mid-thigh biodistribution \[18F\]FTT PET/CT scans over a period of approximately 4 hours. Up to 10 subjects were initially planned for this cohort, however, the first 4 subjects have been enrolled and initial data analysis for these completed. The decision was made to close enrollment for this cohort as we do not believe that we need to complete the up to 10 subjects originally planned for this cohort as the initial data shows consistent and repeatable data that we do not believe would change significantly with the addition of 6 more subjects.

Who Is Running the Clinical Trial?

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

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]

In a study of 42 patients with oesophageal cancer, high uptake of the amino-acid tracer (18)F-FAMT was linked to more advanced cancer stages and lymph node metastasis, indicating its potential as a biomarker for disease progression.

The study confirmed that (18)F-FAMT is specifically transported into tumor cells by the L-type amino-acid transporter 1 (LAT1), and its uptake correlates with cell proliferation and angiogenesis, highlighting LAT1's role in cancer metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological significance of fluorine-18-α-methyltyrosine (FAMT) uptake on PET in patients with oesophageal cancer. Suzuki, S., Kaira, K., Ohshima, Y., et al.[2021]

This pilot study involving 14 patients demonstrated that PSMA 18F-DCFPyl PET/MR imaging can effectively detect ovarian cancer, showing significantly higher tracer uptake in malignant lesions compared to normal and benign ovarian tissues.

The results indicate that PSMA uptake is minimal in benign lesions, suggesting that this imaging technique could help differentiate between malignant and non-malignant ovarian conditions, warranting further research with larger patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distribution of prostate specific membrane antigen (PSMA) on PET-MRI in patients with and without ovarian cancer. Sadowski, EA., Lees, B., McMillian, AB., 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]

In a study of 30 patients with esophageal squamous cell carcinoma, the accumulation of the PET tracer (18)F-FAMT in lymph nodes was correlated with a higher complete response rate to chemoradiotherapy, suggesting its potential as a predictive biomarker for treatment outcomes.

In contrast, (18)F-FDG accumulation did not show a similar correlation, indicating that (18)F-FAMT may be more effective in assessing lymph node involvement and predicting responses to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-[3-¹⁸F]-α-methyltyrosine uptake by lymph node metastasis is a predictor of complete response to CRT in esophageal cancer. Sohda, M., Miyazaki, T., Honjyo, H., et al.[2019]

In a study of 21 women with ovarian cancer, integrated PET/CT imaging significantly improved the localization of cancer lesions, identifying 98% of lesions with definite localization compared to only 44% with PET alone.

PET/CT also reduced the number of equivocal lesions from 51% to 11%, enhancing the accuracy of characterizing lesions as benign or malignant, which is crucial for effective staging and treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-FDG PET and PET/CT in the Localization and Characterization of Lesions in Patients with Ovarian Cancer. Caprio, MG., Capacchione, D., Mainolfi, C., et al.[2021]

An innovative approach using (18)F-FDG PET/CT imaging and a gamma probe during surgery allows for effective localization and verification of tumor resection in patients with recurrent ovarian cancer, enhancing surgical outcomes.

In a study involving three patients, this method successfully confirmed complete resection of tumors in two cases and identified extensive unresectable disease in one case, demonstrating its potential to improve intraoperative decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel perioperative imaging with 18F-FDG PET/CT and intraoperative 18F-FDG detection using a handheld gamma probe in recurrent ovarian cancer. Cohn, DE., Hall, NC., Povoski, SP., et al.[2016]

Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is a valuable imaging tool for guiding clinical management decisions in ovarian cancer patients.

FDG PET/CT is particularly effective for preoperative evaluation of primary ovarian cancer and for assessing recurrence after surgery, which can help improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET/CT in the imaging of ovarian Cancer. O'Connor, OJ., Prakash, P., Cronin, CG., et al.[2022]

References

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

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

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

Biological significance of fluorine-18-α-methyltyrosine (FAMT) uptake on PET in patients with oesophageal cancer. [2021]

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

Distribution of prostate specific membrane antigen (PSMA) on PET-MRI in patients with and without ovarian cancer. [2023]

4. 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]

5. Greece pubmed.ncbi.nlm.nih.gov

L-[3-¹⁸F]-α-methyltyrosine uptake by lymph node metastasis is a predictor of complete response to CRT in esophageal cancer. [2019]

6. Italy pubmed.ncbi.nlm.nih.gov

18F-FDG PET and PET/CT in the Localization and Characterization of Lesions in Patients with Ovarian Cancer. [2021]

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

Novel perioperative imaging with 18F-FDG PET/CT and intraoperative 18F-FDG detection using a handheld gamma probe in recurrent ovarian cancer. [2016]

8. Singapore pubmed.ncbi.nlm.nih.gov

PET/CT in the imaging of ovarian Cancer. [2022]