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

Official title

Integration of FTT-PET and ctDNA to Predict Response to PARP Inhibitor Therapy in Metastatic Prostate Cancer (mPC)

Overview

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.

Interventions

• Drug 1-(4-(2-Fluoroethoxy)phenyl)-8,9-dihiydro-2,7,9a-triazabenzo[cd]azulen-6(7H)-one
  \[18F\]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.
• Device FTT-PET/CT
  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.
• Diagnostic test EnhanceAR-Seq
  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.

Primary outcome measures

• Prediction performance of FTT-PET as measured by concordance index (C-index) [Time frame: 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 [Time frame: 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) [Time frame: 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 [Time frame: 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) [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 outcome measures (10)

• Test-Retest Only: Lin's intra-class correlation coefficient of FTT-PET imaging [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: At baseline and post cycle 1 (estimated total time 28 days)]
• Correlation between FTT-PET imaging and tumor mutation burden (TMBddr) as assessed by Kappa agreement coefficient [Time frame: At baseline and post cycle 1 (estimated total time 28 days)]
• Correlation between FTT-PET imaging and variant allele frequency (VAF) as assessed by Kappa agreement coefficient [Time frame: At baseline and post cycle 1 (estimated total time 28 days)]
• Correlation between FTT-PET imaging and dynamic changes in ctDNA level as assessed by Kappa agreement coefficient [Time frame: At baseline and post cycle 1 (estimated total time 28 days)]
• Correlation between FTT-PET imaging and prostate-specific antigen (PSA) as assessed by Kappa agreement coefficient [Time frame: At baseline and post cycle 1 (estimated total time 28 days)]
• Association of FTT-PET and EnhanceAR-Seq metrics with patient response based on relative risk [Time frame: From enrollment to time of progression (estimated total time 6 months)]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 3 centers

• Washington University School of Medicine — St Louis
• University of Pennsylvania Abramson Cancer Center — Philadelphia
• University of Texas MD Anderson Cancer Center — Houston

Identifiers

NCT: NCT07723651 · 202605165

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗