A Phase 1 Trial for Evaluation of the Safety, Pharmacokinetics, and [18F] Radiation Dosimetry of CTT1057

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to test a novel diagnostic Positron Emission Tomography (PET) imaging agent for safety and biodistribution. The agent binds Prostate Specific Membrane Antigen (PSMA) and is designed to detect prostate tumors.

Detailed Description
-----------------
The sponsor has developed a PET imaging agent, CTT1057, labeled with 18F, that is based on a small molecule core and targets an extracellular region of PSMA with high affinity. Although comparable to other inhibitors in terms of affinity for PSMA, this unique class of phosphoramidate agents are the only known irreversible PSMA inhibitors. Due to its irreversible binding to PSMA and rapid uptake by PSMA-expressing prostate cancer cells, accumulation at the cancer target is expected to be rapid, specific and sensitive. Twenty patients will be enrolled in parallel in two cohorts: (Cohort A) Patients with prostate cancer prior to radical prostatectomy (N = 5). (Cohort B) Patients with evidence of metastatic castration-resistant prostate cancer (N = 15) Participants receive a single intravenous (IV) dose (370 MBq, or 10 mCi) of CTT1057 in this first-in-human trial. Combined PET/MR imaging (prostate + whole body) will be performed following tracer injection. The 5 patients in the pre-prostatectomy cohort will comprise the dosimetry/pharmacokinetic (PK) cohort to establish organ dosimetry and PK profile. Patients in cohort A will undergo planned radical prostatectomy (plus lymph node dissection) within 12 weeks following CTT1057 PET/MR. Patients in cohort B (metastatic prostate cancer) will have the option for metastatic tumor biopsy following CTT1057 PET imaging. The one-time nominal injected dose will be 370 MBq (10 mCi). Estimated mass dose is 20 µg of CTT1057. Dose will be in a volume of 3 - 5 mL, and will be injected intravenously as a bolus injection. Vital signs, adverse event assessment, and 12 lead ECGs will be performed on day 1 before and after dosing.

Official Title
-----------------
A Phase 1 Trial for Evaluation of the Safety, Pharmacokinetics, and [18F] Radiation Dosimetry of CTT1057, a Small Molecule Inhibitor of Prostate Specific Membrane Antigen (PSMA)

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: CTT1057
* Procedure: Prostatectomy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male patients age ≥18 years old Histologically confirmed adenocarcinoma of the prostate Adequate organ function including: - Platelet count of > 50,000/mm3 - Neutrophil count of > 1000/mm3 - Serum Cr < 1.5 x ULN or estimated GFR > 60 ml/min based upon Cockroft-Gault equation - Proteinuria < 1 g/24 hours based upon 24 hour urine collection or spot urine protein/creatinine ratio - AST and ALT < 2.5 x ULN (< 5 x ULN in patients with known liver metastases) - Total bilirubin < 1.5 x ULN (< 3 x ULN in patients with known/suspected Gilbert's disease) ECOG performance status of 0 or 1 Able to provide written informed consent and willing to comply with protocol requirements No contra-indication to MR including severe claustrophobia, incompatible aneurysm clips or cardiac pacemaker For men of childbearing potential, the use of effective contraceptive methods during the trial and within 6 months following radiotracer injection Cohort A only (N = 5 evaluable patients):- Planned radical prostatectomy within 12 weeks following protocol scan - No androgen deprivation, anti-androgen therapy, chemotherapy, or investigational systemic therapy prior to CTT1057 PET imaging Cohort B only:- Presence of at least three distinct metastatic lesions by standard imaging including whole body bone scan + cross-sectional imaging of the abdomen and pelvis obtained within 12 weeks prior to protocol scan - Castration-resistant disease as defined by PCWG2 criteria - Must remain on androgen deprivation therapy for duration of trial if no prior bilateral orchiectomy Exclusion Criteria: Inadequate venous access per assessment of treating health care provider Receipt of radioisotope within 5 physical half lives prior to trial enrollment Prior treatment with alpha radiation therapy (Radium Ra 223 chloride; Xofigo™) during the previous 60 days Have a medical condition or other circumstances that, in the opinion of the investigator would significantly decrease the chances of obtaining reliable data, achieving the study objectives, or completing the trial. Histologic evidence of small cell prostate cancer or neuroendocrine differentiation in > 50% of biopsy tissue

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Pre-prostatectomy patients<br>Patients with prostate cancer prior to radical prostatectomy (N = 5). Single IV dose (370 MBq, or 10 mCi). Combined PET/MR imaging (prostate + whole body) will be performed following tracer injection. Patients in cohort A will undergo radical prostatectomy (plus lymph node dissection) within 12 weeks following CTT1057 PET/MR. | Drug: CTT1057<br>* Single IV dose (370 MBq, or 10 mCi) of CTT1057 followed by combined PET/MR imaging (prostate + whole body).<br>Procedure: Prostatectomy<br>* Radical prostatectomy with lymph node dissection<br>|
| Experimental: Cohort B: Metastatic prostate cancer<br>Patients with evidence of metastatic castration-resistant prostate cancer (N = 15). Single IV dose (370 MBq, or 10 mCi). Combined PET/MR imaging (prostate + whole body) will be performed following tracer injection. Patients in cohort B (metastatic prostate cancer) will have the option for metastatic tumor biopsy following CTT1057 PET imaging. | Drug: CTT1057<br>* Single IV dose (370 MBq, or 10 mCi) of CTT1057 followed by combined PET/MR imaging (prostate + whole body).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event frequency as graded by Common Toxicity Criteria version 4.03 |  | 7 days from time of injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Organ dosimetry/tissue uptake of CTT1057 as measured by PET/MR imaging of prostate cancer |  | Up to six hours from time of injection | 
| Pharmacokinetic profile of CTT1057 as measured by radiotracer detection in blood samples |  | Up to four hours from time of injection | 
| Level of CTT1057 uptake on PET/MR imaging of localized prostate cancer with PSMA protein expression by immunohistochemistry from subsequent radical prostatectomy specimens |  | 12 weeks | 
| Optimal Standardized Uptake Value (SUV) ratio threshold on CTT1057 PET/MR for discriminating tumor pathology from primary prostate cancer tissue |  | 4 hours | 
| Sensitivity and specificity of CTT1057 PET imaging on a lesion-by-lesion basis as compared with standard imaging in metastatic prostate cancer |  | 4 hours | 
| Number of positive lesions on CTT1057 PET/MR in subjects with equivocal or negative conventional imaging scans |  | 4 hours | 
| Location of positive lesions on CTT1057 PET/MR in subjects with equivocal or negative conventional imaging scans |  | 4 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
prostate cancer, prostate specific membrane antigen, prostate neoplasms, metastatic prostate cancer, prostatic hyperplasia