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.
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.
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.
Single group
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.
FTT-PET/CT
DeviceA 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.
EnhanceAR-Seq
Diagnostic testPatients 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.
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).
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.
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).
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.
Test-Retest Only: Lin's intra-class correlation coefficient of FTT-PET imaging
Defined as concordance between a new test or measurement (Y) and a gold standard test or measurement (X). This statistic quantifies the agreement between these two measures of the same variable. Ranges from -1 to 1, with perfect agreement at 1.
Correlation between FTT-PET imaging and tumor mutation burden (TMBddr) as assessed by Spearman or Pearson correlation coefficient
TMBddr is the number of genetic mutation in tumor cells that can affect patient response and will be assessed through EnhanceAR-Seq ctDNA. Spearman's correlation coefficient evaluates the association and the association's direction between two ranked continuous variables. Spearman's correlation coefficient ranges from -1 to 1, with a negative number indicating a negative relationship between variables and a positive number indicating a positive relationship between variables. Values closer to zero indicate a weak relationship. Pearson's correlation coefficient is a measure that evaluates the association between two continuous variables with the assumption that the variables have a linear relationship. Pearson's correlation coefficient ranges from -1 to 1, with a negative number indicating a negative relationship between variables and a positive number indicating a positive relationship between variables. Values closer to zero indicate a weak relationship.
Correlation between FTT-PET imaging and variant allele frequency (VAF) as assessed by Spearman or Pearson correlation coefficient
VAF represents the fraction of variant sequencing reads within a genetic locus and will be assessed through EnhanceAR-Seq ctDNA. Spearman's correlation coefficient evaluates the association and the association's direction between two ranked continuous variables. Spearman's correlation coefficient ranges from -1 to 1, with a negative number indicating a negative relationship between variables and a positive number indicating a positive relationship between variables. Values closer to zero indicate a weak relationship. Pearson's correlation coefficient is a measure that evaluates the association between two continuous variables with the assumption that the variables have a linear relationship. Pearson's correlation coefficient ranges from -1 to 1, with a negative number indicating a negative relationship between variables and a positive number indicating a positive relationship between variables. Values closer to zero indicate a weak relationship.
Correlation between FTT-PET imaging and dynamic changes in ctDNA levels as assessed by Spearman or Pearson correlation coefficient
Dynamic changes in ctDNA refer to measurable changes in circulating tumor DNA in patient's blood over time and will be assessed through EnhanceAR-Seq ctDNA. Spearman's correlation coefficient evaluates the association and the association's direction between two ranked continuous variables. Spearman's correlation coefficient ranges from -1 to 1, with a negative number indicating a negative relationship between variables and a positive number indicating a positive relationship between variables. Values closer to zero indicate a weak relationship. Pearson's correlation coefficient is a measure that evaluates the association between two continuous variables with the assumption that the variables have a linear relationship. Pearson's correlation coefficient ranges from -1 to 1, with a negative number indicating a negative relationship between variables and a positive number indicating a positive relationship between variables. Values closer to zero indicate a weak relationship.
Click on the lead sponsor to view all of their trials.
Washington University School of Medicine
Lead sponsor
National Cancer Institute (NCI)
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
