Imaging and Genomic Biomarkers to Predict Response in Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

Pilot Study to Identify Radiogenomic Biomarkers to Predict Early Treatment Response to Androgen Deprivation Therapy and Radiation Therapy in High Risk Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05477823
• Other study ID #: UW20099
• Secondary ID: 2022-0493Protoco
• Status: Recruiting
• Phase: Early Phase 1
• Start date: March 8, 2023
• Est. completion date: August 2027

Study information

• Verified date: March 2024
• Source: University of Wisconsin, Madison
• Contact: Cancer Connect
• Phone: 800-622-8922
• Email: clinicaltrials[@]cancer.wisc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the imaging and gene expression biomarkers in prostate cancer. Participants have high-risk prostate cancer and have indicated they will undergo external beam radiation therapy, brachytherapy, and androgen deprivation therapy (EBRT+BTX+ADT). Participants can expect to be in this study for up to 5 years.

Description:

This is a pilot study to prospectively investigate potential predictive imaging and genomic biomarkers for patients with high-risk prostate cancer treated with standard of care EBRT + BTX + ADT. The primary imaging modalities that will be evaluated will be PSMA positron emission tomography (PET) and multi-parametric magnetic resonance imaging (MRI). Pre-treatment PET/MRI scans will also be obtained as part of standard of care prior to study enrollment. Response will be assessed on a mid-treatment PET/MRI scan obtained for research purposes after completion of EBRT but prior to brachytherapy boost. PET/CT (computerized tomography) may be used instead if PET/MRI is not technically possible. Imaging response will be compared to pathology from image-directed prostate biopsies taken at the time of the brachytherapy boost. The primary genomic marker that will be evaluated is a clinically available gene-expression array, Decipher, that will be obtained as part of standard of care prior to study enrollment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 2027
• Est. primary completion date: August 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18
• Histologically confirmed adenocarcinoma of the prostate
• Cancer classified as high-risk or very high-risk by National Comprehensive Cancer Network (NCCN) criteria: Grade group =4, PSA >20, or primary tumor stage =T3a
• ECOG performance status 0-1
• Agreed to undergo EBRT, high dose rate (HDR) brachytherapy boost, and 6-36 months of ADT as part of standard of care therapy prior to study enrollment
• Able to undergo a HDR brachytherapy implant: Pre-radiation IPSS score =20 with or without medical management; prostate =60 cc as measured by MRI or ultrasound; no prior trans-urethral resection of prostate (TURP); and, median lobe extending into the bladder <1 cm
• No prior or concurrent malignancy unless disease-free for at least 5 years

Exclusion Criteria:

• Evidence of regional or distant metastatic disease on pre-treatment bone scan, pelvic MRI, and/or CT of the abdomen/pelvis
• Prior pelvic radiation therapy

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Radiation:
• External beam radiation therapy
Standard of care EBRT
• Prostate brachytherapy boost
Standard of care BTX

Drug:
• Androgen deprivation therapy
Standard of care ADT

Diagnostic Test:
• Positron emission tomography (PET)/magnetic resonance imaging (MRI)
Pelvic PET scanning with tracer will take approximately 45 minutes. This will be followed by the injection of a contrast agent followed by whole body PET/MRI scanning which will take approximately 30 minutes.

Locations

Country	Name	City	State
United States	University of Wisconsin	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
University of Wisconsin, Madison

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in cancer gene expression during therapy	Evaluate changes in gene expression from pre- to mid-treatment, and their association with response to therapy.	Baseline and mid-treatment (approximately 3 months into treatment)
Other	Prognostic significance of higher order radioman metrics	Higher order radiomic metrics (e.g. measures of PET lesion heterogeneity obtained using open-source radiomic software) will be assessed as potential predictive markers for pathologic treatment response (measured as outlined in Outcome 3) to ADT and EBRT.	Baseline and mid-treatment (approximately 3 months into treatment)
Primary	Imaging markers for mid-treatment response	Evaluate prostate specific membrane antigen (PSMA) PET/MRI for imaging biomarkers that predict mid-treatment response to ADT and EBRT to identify participants at risk for poor response to radiation therapy and ADT.	Mid-treatment (approximately 3 months into treatment)
Secondary	Genomic signatures correlated with imaging response	Determine if the Decipher and PORTOS genomic scores (high vs low) and basal/luminal genomic subtypes are correlated with change in PSMA standardized uptake value (SUV) pre-to-mid-treatment.	Baseline and mid-treatment (approximately 3 months into treatment)
Secondary	Establish a correlation between PET imaging response and pathologic response	PET images will be assessed for response using change in SUV in order to establish a correlation between imaging response and pathologic response to ADT and EBRT on a lesion-by-lesion basis. Pathologic response will be evaluated considering change in percent core involvement, prostate cancer epithelial/stromal (E/S) ratio, PSMA, CC3 and Ki67 expression. Concordance will be assessed using the Kappa statistic.	Baseline and mid-treatment (approximately 3 months into treatment)
Secondary	Establish a correlation between MRI imaging response and pathologic response	MR images will be assessed for response using change in apparent diffusion coefficient (ADC) in order to establish a correlation between imaging response and pathologic response to ADT and EBRT on a lesion-by-lesion basis. Pathologic response will be evaluated as described in Outcome 3. Concordance will be assessed using the Kappa statistic.	Baseline and mid-treatment (approximately 3 months into treatment)
Secondary	Imaging and genomic markers for prostate specific antigen (PSA) recurrence.	Determine if imaging and genomic markers that predict for mid-treatment pathologic response also predict PSA recurrence.	Baseline, 3 months post therapy, every 6 months for 5 years
Secondary	Evaluate blood-based biomarkers for treatment response.	Messenger RNA from circulating tumor cells (CTCs) will be extracted to determine if presence of androgen receptor variants and a neuroendocrine prostate cancer signature (a score based upon the expression of a set of genes) is correlated with pathologic response (determined as outlined in Outcome 3).	Baseline and mid-treatment (approximately 3 months into treatment)