[18F]Fluorthanatrace - Positron Emission Tomography (FTT-PET) and ctDNA to Predict Response to PARP Inhibitor Therapy in Metastatic Prostate Cancer (mPC)

NCT07723651 | Not Yet Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: 202605165
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 3

Brief Summary

This multicenter center, open-label, baseline-controlled diagnostic imaging study designed to assess the use of Fluorthanatrace-Positron Emission tomography (FTT-PET) as a PARP inhibitor (PARPi) therapy predictive imaging biomarker and the use of EnhanceAR-Seq (ctDNA) in predicting response to therapy and to identify genomic alterations associated with resistance. Furthermore, to correlate changes in ctDNA and imaging (FTT-PET and standard of care imaging) to understand the dynamics of tumor response.

Conditions

Metastatic Prostate Cancer; Prostate Cancer

Keywords

PARP; FTT; PET; Prostate cancer

Outcome Measures

Primary Outcomes (12)

• Prediction performance of FTT-PET as measured by concordance index (C-index)

  Prediction performance of FTT-PET in predicting participant response to PARPi therapy will be assessed by concordance index (C-index). The C-index is mathematically calculated as the number of concordant pairs divided by the number of comparable pairs. A C-index of 1 indicates perfect ranking, values close to 0.5 indicate random prediction, and values between 0.5 and 1 suggest some predictive ability (a value below 0.5 can be reversed by switching the response's 0 and 1 labels).

  At baseline prior to PARPi therapy and post cycle 1 (estimated total time 28 days)

• Prediction performance of FTT-PET as measured by area under the receiver operating characteristic (ROC) curve

  Prediction performance of FTT-PET in predicting participant response to PARPi therapy will be assessed by the area under the ROC curve. The ROC curve is a graphical plot that illustrates the performance of a model at various threshold settings and the area under the curve (AUC) is a single scalar value between 0 and 1 that summarizes the model performance. A higher AUC value indicates better performance.

  At baseline prior to PARPi therapy and post cycle 1 (estimated total time 28 days)

• Prediction performance of EnhanceAR-Seq ctDNAas measured by concordance index (C-index)

  Prediction performance of EnhanceAR-Seq ctDNA analysis in predicting participant response to PARPi therapy will be assessed by concordance index (C-index). The C-index is calculated as the number of concordant pairs divided by the number of comparable pairs. A C-index of 1 indicates perfect ranking, values close to 0.5 indicate random prediction, and values between 0.5 and 1 suggest some predictive ability (a value below 0.5 can be reversed by switching the response's 0 and 1 labels).

  At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), 12 weeks after start of PARPi therapy, and at progression if applicable (estimated total time 6 months)

• Prediction performance of EnhanceAR-Seq ctDNA as measured by area under the receiver operating characteristic (ROC) curve

  Prediction performance of EnhanceAR-Seq ctDNA analysis in predicting participant response to PARPi therapy will be assessed by the area under the ROC curve. The ROC curve is a graphical plot that illustrates the performance of a model at various threshold settings and the area under the curve (AUC) is a single scalar value between 0 and 1 that summarizes the model performance. A higher AUC value indicates better performance.

  At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), 12 weeks after start of PARPi therapy, and at progression if applicable (estimated total time 6 months)

• Prediction performance of FTT-PET and EnhanceAR-Seq ctDNA collectively as measured by concordance index (C-index)

  Prediction performance of FTT-PET and EnhanceAR-Seq ctDNA analysis collectively in predicting participant response to PARPi therapy will be assessed by concordance index (C-index). The C-index is calculated as the number of concordant pairs divided by the number of comparable pairs. A C-index of 1 indicates perfect ranking, values close to 0.5 indicate random prediction, and values between 0.5 and 1 suggest some predictive ability (a value below 0.5 can be reversed by switching the response's 0 and 1 labels).

  At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), and at progression if applicable (estimated total time 6 months)

• Prediction performance of FTT-PET and EnhanceAR-Seq ctDNA collectively as measured by area under the receiver operating characteristic (ROC) curve

  Prediction performance of FTT-PET and EnhanceAR-Seq ctDNA analysis collectively in predicting participant response to PARPi therapy will be assessed by the area under the ROC curve. The ROC curve is a graphical plot that illustrates the performance of a model at various threshold settings and the area under the curve (AUC) is a single scalar value between 0 and 1 that summarizes model performance. A higher AUC value indicates better performance.

  At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), and at progression if applicable (estimated total time 6 months)

• Sensitivity of EnhanceAR-Seq ctDNA in identifying mPC patients who respond to PARPi therapy

  Sensitivity is calculated as the proportion of true positives divided by the sum of true positives and false negatives. The area under the Receiver Operating Characteristic (ROC) curve will be calculated to identify the optimal cutpoint on the ROC corresponding to the maximized Youden index to evaluate sensitivity. The ROC curve is a graphical plot that illustrates the performance of a model at various threshold settings and the area under the curve (AUC) is a single scalar value between 0 and 1 that summarizes model performance. A higher AUC value indicates better performance.

  At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), 12 weeks after start of PARPi therapy, and at progression if applicable (estimated total time 6 months)

• Specificity of EnhanceAR-Seq ctDNA in identifying mPC patients who respond to PARPi therapy

  Specificity is calculated as the proportion of true negatives divided by the sum of true negatives and false positives. The area under the Receiver Operating Characteristic (ROC) curve will be calculated to identify the optimal cutpoint on the ROC corresponding to the maximized Youden index to evaluate specificity. The ROC curve is a graphical plot that illustrates the performance of a model at various threshold settings and the area under the curve (AUC) is a single scalar value between 0 and 1 that summarizes the performance of model. A higher AUC value indicates better performance.

  At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), 12 weeks after start of PARPi therapy, and at progression if applicable (estimated total time 6 months)

• Positive predictive value (PPV) of EnhanceAR-Seq ctDNA in identifying mPC patients who respond to PARPi therapy

  PPV is calculated as the number of true positives divided by the sum of the number of true positives and number of false positives. The area under the Receiver Operating Characteristic (ROC) curve will be calculated to identify the optimal cutpoint on the ROC corresponding to the maximized Youden index to evaluate PPV. The ROC curve is a graphical plot that illustrates the performance of a model at various threshold settings and the area under the curve (AUC) is a single scalar value between 0 and 1 that summarizes model performance. A higher AUC value indicates better performance.

  At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), 12 weeks after start of PARPi therapy, and at progression if applicable (estimated total time 6 months)

• Negative predictive value (NPV) of EnhanceAR-Seq ctDNA in identifying mPC patients who respond to PARPi therapy

  NPV is calculated as the number of true negatives divided by the sum of the number of true negatives and number of false negatives. The area under the Receiver Operating Characteristic (ROC) curve will be calculated to identify the optimal cutpoint on the ROC corresponding to the maximized Youden index to evaluate NPV. The ROC curve is a graphical plot that illustrates the performance of a model at various threshold settings and the area under the curve (AUC) is a single scalar value between 0 and 1 that summarizes model performance. A higher AUC value indicates better performance.

  At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), 12 weeks after start of PARPi therapy, and at progression if applicable (estimated total time 6 months)

• Predictive performance improvement as measured by change in concordance index of FTT-PET and EnhanceAR-seq ctDNA compared to only FTT-PET or only EnhanceAR-seq ctDNA

  Prediction performance of FTT-PET and EnhanceAR-seq ctDNA in predicting participant response to PARPi therapy will be assessed by the concordance index (C-index). The C-index is calculated as the number of concordant pairs divided by the number of comparable pairs. A C-index of 1 indicates perfect ranking, values close to 0.5 indicate random prediction, and values between 0.5 and 1 suggest some predictive ability prediction (a value below 0.5 can be reversed by switching the response's 0 and 1 labels).

  At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), 12 weeks after start of PARPi therapy, and at progression if applicable (estimated total time 6 months)

• Predictive performance improvement as measured by area under the receiver operating characteristic (ROC) curve of FTT-PET and EnhanceAR-seq ctDNA compared to only FTT-PET or only EnhanceAR-seq ctDNA

  Prediction performance of FTT-PET and EnhanceAR-seq ctDNA in predicting participant response to PARPi therapy will be assessed by the area under the ROC curve. The ROC curve is a graphical plot that illustrates the performance of a model at various threshold settings and the area under the curve (AUC) is a single scalar value between 0 and 1 that summarizes model performance. A higher AUC value indicates better performance.

  At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), 12 weeks after start of PARPi therapy, and at progression if applicable (estimated total time 6 months)

Secondary Outcomes (10)

• Test-Retest Only: Lin's intra-class correlation coefficient of FTT-PET imaging

  At baseline prior to PARPi therapy, at retest scan 1-14 days after baseline scan, and post-cycle 1 (estimated total time 28 days)

• Correlation between FTT-PET imaging and tumor mutation burden (TMBddr) as assessed by Spearman or Pearson correlation coefficient

  At baseline and post cycle 1 (estimated total time 28 days)

• Correlation between FTT-PET imaging and variant allele frequency (VAF) as assessed by Spearman or Pearson correlation coefficient

  At baseline and post cycle 1 (estimated total time 28 days)

• Correlation between FTT-PET imaging and dynamic changes in ctDNA levels as assessed by Spearman or Pearson correlation coefficient

  At baseline and post cycle 1 (estimated total time 28 days)

• Correlation between FTT-PET imaging and prostate-specific antigen (PSA) levels as assessed by Spearman or Pearson correlation coefficient

  At baseline and post cycle 1 (estimated total time 28 days)

Study Arms (1)

FTT-PET/CT

EXPERIMENTAL

Participants will undergo two FluorThanatrace (FTT) Positron Emission Tomography/Computed tomography (PET/CT) scans; one at baseline prior to starting standard of care (SOC) PARP inhibitor (PARPi) therapy and one two weeks after initiation of PARPi therapy. Each cycle of PARPi therapy is 28 days. Blood samples for EnhanceAR-Seq ctDNA analysis will be collected from participants at baseline prior to therapy, post cycle 1,12 weeks after PARPi initiation, and at time of disease progression. Eight participants will undergo an additional FTT-PET/CT prior to initiation of PARPi therapy.

Drug: 1-(4-(2-Fluoroethoxy)phenyl)-8,9-dihiydro-2,7,9a-triazabenzo[cd]azulen-6(7H)-one; Device: FTT-PET/CT; Diagnostic Test: EnhanceAR-Seq

Interventions

FTT-PET/CT DEVICE

A small intravenous (IV) catheter will be placed in the arm vein according to site's standard practice to allow injection of FTT. Approximately sixty minutes following administration of approximately 10 mCi of the radiotracer FTT, patients will undergo standard body PET/CT imaging.

FTT-PET/CT

EnhanceAR-Seq DIAGNOSTIC_TEST

Patients will undergo approximately 30 mL of peripheral blood sample collection to be used for analysis. For each sample, EnhanceAR-Seq will be performed on each of these samples, with somatic genomic alteration calling performed in plasma cell-free DNA with removal of background non-tumor variants using matched plasma-depleted whole blood germline samples.

FTT-PET/CT

1-(4-(2-Fluoroethoxy)phenyl)-8,9-dihiydro-2,7,9a-triazabenzo[cd]azulen-6(7H)-one DRUG

\[18F\]fluorthanatrace (FTT) is a positron emitting radiopharmaceutical that is administered as an intravenous (IV) solution via injection at a prescribed dose of 10mCi. A lesser dose may be injected if complete imaging data could be generated.

Also known as: FTT, [18F]FluorThanatrace, [18F]FTT

FTT-PET/CT

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult male patients 18 years of age or older
• mCRPC with confirmed germline or somatic HRR (such as ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C for Talazoparib/enzalutamide and ATMm, BRCA1m, BRCA2m, BARD1m, BRIP1m, CDK12m, CHEK1m, CHEK2m, FANCLm, PALB2m, RAD51Bm, RAD51Cm, RAD51Dm, RAD54Lm; gBRCA1m, gBRCA2m; ATMm, BRCA1m, BRCA2m for Olaparib +/- abiraterone) mutations who are scheduled for SOC PARPi therapy.
• Lesion size of at least 1.0 cm in longest dimension by imaging. If non-measurable, lesion needs to be clearly detected on other imaging studies such as bone scintigraphy, FDG-PET, PSMA-PET or MRI.
• On continuous androgen deprivation therapy (ADT) with appropriately suppressed castrate testosterone levels of \< 50 ng/dL, or prior bilateral orchiectomy.
• Serum PSA of 2 ng/mL or greater.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Able to give informed consent

You may not qualify if:

• Receipt of prior PARP inhibitor therapy in any disease setting.
• Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of the other cancer that is active at the time of enrollment.
• Unable to tolerate approximately 30 min (total time) of PET/CT imaging.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Farrokh Dehdashti, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Farrokh Dehdashti, MD

CONTACT

314-362-1474; dehdashtif@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2026
• First Posted: July 23, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 31, 2032
• Study Completion (Estimated): March 31, 2032
• Last Updated: July 23, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be available as soon as possible, but no later than the time of publication or the end of the funding period, whichever comes first. The duration of preservation and sharing of the data will be determined based on timelines established by respective NCI repositories.

Locations

US (3)