Progressive Prostate cancer MedDRA version: 18.1 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Fluorinated dihydrotestosterone
Product Code: FDHT
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: 18F-fluorodihydrotestosterone
Other descriptive name: 18F- fluorodihydr
Sponsors
The Royal Marsden NHS Foundation Trust
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1 Patients with histologically confirmed prostate cancer (Male =18 years old, no upper limit) 2 Progressive disease manifest by either: 2.1 Imaging modalities: Bone Imaging: New osseous lesions on bone imaging (bone scintigraphy or NaF PET scan) and/or MRI or CT: An increase in measurable soft tissue disease, or the appearance of new sites of disease. Or 2.2. Biochemical progression: A minimum of three rising PSA values from a baseline that are obtained 1 week or more apart, or 2 measurements 2 or more weeks apart. 3 Visible lesions by CT, bone imaging or MRI, consistent with disease. 4 Informed consent: able and willing to give written informed consent and to comply with the study protocol procedures. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 65
Exclusion criteria
Exclusion criteria: 1. Previous anaphylactic reaction to 18F-FDHT. 2. Hepatic: Bilirubin > 1.5 x upper limit of normal (ULN), AST/ALT >2.5 x ULN, albumin 2.5 x ULN IF Alkaline phosphatase >2.5 x ULN. 3. Renal: Creatinine > 1.5 x ULN or creatinine clearance <60mL/min.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of this study are: 1 - To study the accumulation and biodistribution of 18F-FDHT in patients with progressive prostate cancer. 2 - The accumulation and location of 18F-FDHT activity will be assessed on a site by site basis and correlated with radionuclide bone scan, Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). 3 - The kinetics, metabolism, and bio-distribution will be assessed. ;Secondary Objective: The secondary objectives are: 1 - To define the relationship between 18F-FDHT uptake and tumour diffusivity as assessed by MRI. 2 - To study changes in 18F-FDHT accumulation over time in patients treated with: • Abiraterone acetate • Castration and other hormones • Chemotherapy. The tertiary objective: 1 - To preliminarily determine the relationship between 18F-FDHT uptake and tissue analyses of AR expression (tissue will not be acquired under this protocol at RM). ;Timepoint(s) of evaluation of this end point: Please see above.;Primary end point(s): Primary endpoints:(this analysis is based on the total trial data collected from the 105 patients recruited across sites) For each patient in cohort 1 (30 patients) and each lesion imaged within the field of view of a dynamic 18F-FDHT PET scan, we will fit a 2-compartment, first-order model and determine k3 values (a measure of androgen receptor density) using a metabolite corrected, venous blood-sample-scaled, population-based input function. Historically, we have seen an average of 18 lesions per patient for mCRPC patients. The general estimating equation approach, based on an ordinal regression model, will be used to determine at the lesion level the relationship between k3 and the concentration of AR within the lesion as determined from subsequently acquired biopsy samples of these same lesions. The general estimating equation approach is used to account for the multiple time points (15, 30, 45, 60, 90, and 120 minutes from 18F-FDHT inj | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: Areas of abnormal 18F-FDHT uptake on PET will be visually correlated on WB-MRI for the presence of abnormal MR signal intensity (on T1 and fat/water sequences), diffusion (on DW-MR images and ADC maps) or perfusion (raw DCE images and parametric maps). Quantitative MRI measurements from diffusion-weighted imaging (ADC) and DCE-MRI (Ktrans, kep, ve) will be calculated and correlated to quantitative and semi-quantitative PET metrics obtained from areas of abnormal 18F-FDHT uptake. Lesions detected on MRI without corresponding 18F-FDHT accumulation on PET will also be recorded. For expansion cohorts 2-4 patients (at least 30 patients) will be treated with abiraterone acetate for 28 days after the second scan. At the conclusion of the treatment a third scan is proposed and an initial examination of the prognostic value of the change in18F-FDHT PET and MRI from the second to the third scan will be undertaken. The two other endpoints will be PSA progression free survival time and radiographic progression free survival time. The Cox proportional hazards model will be employed to study the prognostic value of the change in 18F-FDHT and MRI parameters. A landmark analysis, starting after the completion of the abiraterone acetate treatment, will be performed. ;Timepoint(s) of evaluation of this end point: Please see above. | — |
Countries
Australia, Netherlands, United Kingdom, United States
Contacts
Public ContactChua
The Royal Marsden NHS foudation Trust
Outcome results
None listed