A Multi-Center, Open-Label, Randomized Phase 2 Study of Copper Cu 64 PSMA I&T Injection in Patients With Histologically Proven Metastatic Prostate Cancer
Phase: PHASE2
Conditions: Metastasis From Malignant Tumor of Prostate (Disorder)
Sponsor: Curium US LLC



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SOP 
Standard Operating Procedure 
SUVmax 
Maximum standard uptake value 
UP 
Unanticipated problem 
US 
United States 
VOI 
Volume of interest 
WHO 
World Health Organization 
 
 
 
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PROTOCOL SYNOPSIS 
Title of Study 
A Multi-Center, Open-Label, Randomized Phase 1/2 Study of Copper  
Cu 64 PSMA I&T Injection in Patients with Histologically Proven 
Metastatic Prostate Cancer 
Phase of 
Clinical Trial 
Phase 1/2  
Indication 
Detection and localization of recurrent prostate cancer in men with 
biochemical recurrence based on elevated blood prostate specific antigen 
(PSA) levels following prior treatment. 
Number of Sites 5-10 
Drug Product 
Copper Cu 64 PSMA I&T  
Study 
Objectives 
Phase 1 
Primary Objectives:  
The primary objectives of the Phase 1 portion of this study are: 
 
To assess the safety and determine radiation dosimetry estimates 
following intravenous administration of 5, 7, and 9 mCi doses of copper 
Cu 64 PSMA I&T injection in patients with recurrent prostate cancer. 
Safety will be assessed by monitoring adverse events, clinical chemistry, 
hematology, urinalysis, vital signs, ECG, and determination of radiation 
absorbed dose estimates.  
 
To assess the PET/CT image quality following intravenous 
administration of 5, 7, and 9 mCi doses of copper Cu 64 PSMA I&T 
injection to determine an acceptable dose for obtaining diagnostic quality 
PET/CT images. 
Phase 2 
Primary Objectives:  
The primary objectives of the Phase 2 portion of this study are:  
 
To determine the region-level correct localization rate (CLR) of 
copper Cu 64 PSMA I&T injection PET/CT imaging for the detection of 
recurrent metastatic prostate cancer at 1 hour and 4 hours post injection. 
The CLR is defined as the percentage of regions containing at least one 
true PET positive lesion, with exactly localized correspondence between 
PET/CT imaging and the Composite Reference Standard regardless of any 
co-existent false positive findings, within the same region, out of all 
regions containing at least one PET positive finding. 
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To determine the patient-level correct detection rate (CDR) of 
copper Cu 64 PSMA I&T injection PET/CT imaging for the detection of 
recurrent metastatic prostate cancer at 1 hour and 4 hours post injection. 
The CDR is defined as the percentage of patients who have at least one 
true PET positive lesion, with exactly localized correspondence between 
PET imaging and the Composite Reference Standard, regardless of any co-
existent false positive findings, out of all patients who are scanned.  
 
To assess the safety of copper Cu 64 PSMA I&T injection in 
patients with recurrent prostate cancer. Safety will be assessed by 
monitoring adverse events, clinical chemistry, hematology, urinalysis, 
ECG, and vital signs. 
Secondary Objective:  
 
To compare the diagnostic quality of PET/CT images obtained at 1 
hour and 4 hours post copper Cu 64 PSMA I&T injection. 
Study Design 
This is a prospective, open-label Phase 1/2 study to evaluate copper Cu 64 
PSMA I&T injection for PET/CT imaging in patients with recurrent 
metastatic prostate cancer after radical prostatectomy or radiation therapy.  
Phase 1 
The Phase 1 portion of the study will include a total of 12 patients with 
metastatic prostate cancer. Patients will be randomized into three groups of 
four patients. Patients in each group will receive a single intravenous dose 
of 5, 7, or 9 mCi of copper Cu 64 PSMA I&T. Whole-body PET/CT 
images will be acquired at 1 hour ± 15 minutes, 4 hours ± 0.5 hours, and 
24 hours ± 2.0 hours post-injection to determine radiation absorbed dose 
estimates.  
The 1 hour and 4-hour PET/CT images will be evaluated independently by 
three readers blinded to all patient information and dose administered to 
assess the quality of the images (24 PET/CT image sets total). The 
assessments will be used to determine an acceptable dose to be 
administered for the Phase 2 study. 
Phase 2 
The Phase 2 portion of the study will include a separate group of 26 
patients with metastatic prostate cancer. Each patient will be administered 
the same intravenous dose of copper Cu 64 PSMA I&T injection 
determined in the Phase 1 study. PET/CT images will be acquired for all 
patients at 1 hour ± 15 minutes and 4 hours ± 30 minutes post copper Cu 
64 PSMA I&T injection.  
The PET/CT images will be interpreted independently by three readers 
blinded to all patient information. Each patient study will be assessed and 
scored for the detection of prostate cancer. Specifically, each reader will 
categorize images as “Disease” or “No Disease” based only on tumor 
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uptake of copper Cu 64 PSMA-I&T in each of the four regions: 1) prostate 
bed or prostate gland, 2) lymph nodes (pelvic and extra pelvic), 3) bone, 
and 4) viscera/soft tissue. Analysis of the reads will be used for 
determination of the CLR and CDR for 1 hour and 4-hour post-injection 
imaging of copper Cu 64 PSMA I&T PET/CT by comparison to the 
Composite Reference Standard.  
Study 
Population 
 
 
The study will include patients with metastatic proven prostate 
adenocarcinoma. 
Phase 1:  Total of 12 patients. 
Inclusion Criteria: 
1. Patients with histologically proven prostate adenocarcinoma.  
2. Prior radical prostatectomy or radiation therapy with curative 
intent. 
3. Recurrence of disease, defined as: 
a. Prior Radical Prostatectomy: PSA > 0.2 ng/mL, or 
b. Prior Radiation Therapy: 2 ng/mL rise in PSA over post-
treatment nadir. 
4. Patients with at least one extraprostatic site of disease suspected 
based on prior imaging or diagnosed by biopsy. 
5. Age greater than or equal to 18 years. 
6. Able to understand and provide signed written informed consent. 
Exclusion Criteria: 
1. Body weight greater than 350 lb. (158 kg). 
2. Investigational therapy within the past 30 days. 
3. Creatinine clearance (ClCr) less than 30 mL/min. 
4. Participants who are capable of fathering a child and who are 
unwilling to take precautions to prevent pregnancy. 
Phase 2: Total of 26 patients.  
Inclusion Criteria: 
1. Patients with histologically proven prostate adenocarcinoma.  
2. Prior radical prostatectomy or radiation therapy with curative 
intent. 
3. Recurrence of disease defined as: 
a. Prior Radical Prostatectomy: PSA > 0.2 ng/mL, or 
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b. Prior Radiation Therapy: 2 ng/mL rise in PSA over post-
treatment nadir 
4. Patients with at least one extraprostatic site of disease suspected 
based on prior imaging or diagnosed by biopsy. 
5. Age greater than or equal to 18 years. 
6. Able to understand and provide signed written informed consent. 
Exclusion Criteria: 
1. Androgen deprivation therapy (ADT) or other therapies targeting 
the androgen pathway unless subject has a rising PSA level. 
2. Body weight greater than 350 lb (158 kg). 
3. Investigational therapy within the past 30 days. 
4. Creatinine clearance (ClCr) less than 30 mL/min. 
5. Participants who are capable of fathering a child and who are 
unwilling to take precautions to prevent pregnancy. 
 
Phase 1 Study 
Procedures 
A total of 12 patients will be randomly assigned to one of three groups, 
four patients per group, to receive a single intravenous injection of 5, 7, or 
9 mCi of copper Cu 64 PSMA I&T. 
Screening:  
All patients will be screened to ensure they meet all inclusion and no 
exclusion criteria for enrollment in the study. Written informed consent 
will be obtained for all patients enrolled in the study. 
Baseline Assessments:  
Routine clinical chemistry, hematology, and urinalysis will be obtained for 
all patients prior to dosing. PSA will also be obtained for all patients prior 
to dosing. 
Medical history and physical examination will be performed prior to 
dosing. This will include information on the history of the prostate cancer. 
Concomitant medication history will also be obtained. 
A baseline 12-lead ECG will be obtained prior to dosing. Vital signs 
including heart rate, respiratory rate, and blood pressure will be assessed 
prior to dosing. 
Randomization: 
Patients will be randomized to receive a single dose of 5, 7 or 9 mCi of 
copper Cu 64 PSMA I&T injection.  
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Pharmacokinetic/Radiation Absorbed Dose: 
Whole body PET/CT scans will be acquired at 1 hour ± 15 minutes, 4 
hours ± 30 minutes, and 24 hours ± 2.0 hours post-injection.  CT scans will 
be acquired for attenuation correction and anatomical reference. Images 
will be acquired using calibrated time-of-flight mode using digital 
scanners. For calculation of radiation absorbed dose estimates, volumes of 
interest (VOI) will be delineated for the kidneys, liver, lungs, spleen, 
urinary bladder, salivary glands, and total body. Image count values will be 
corrected for radioactive decay, scanner response, start/stop times, and net 
injected dose. The remaining activity will be assumed to be distributed 
homogeneously throughout the body after adjusting for activity in the 
organs, blood, and voided urine. Organ-specific and whole-body radiation 
dose analysis will be performed using OLINDA/EXM software, following 
Medical Internal Radiation Dose (MIRD) guidelines.  
Voided urine activity values will be accounted for in the dosimetry 
analysis by collection of all urine for 0-1 hour and 1-4 hour intervals post-
injection. The total voided urine volume for each interval will be measured 
and the total radioactivity calculated by comparison to a calibrated 
standardized sample or per Site’s standard methods. Calibrated urine 
voiding curves will be determined and included in the dosimetry analysis.  
Venous blood samples will be collected prior to copper Cu 64 PSMA I&T 
injection and at 1 hour, 2 hours, 4 hours and 24 hours post-injection. The 
radioactivity concentration in the blood samples will be determined on a 
per-milliliter basis using a calibrated standard measured in a well counter 
for dosimetry analysis or per Site’s standard methods. No metabolite 
analysis will be performed on the blood or urine samples.  
Estimates of radiation absorbed dose will be calculated for all patients with 
the data from the VOI analysis at each imaging timepoint.  
Dose-Range Evaluation: 
The 1 hour and 4-hour post-injection PET/CT images for all patients will 
be evaluated for diagnostic image quality by three independent readers 
blinded to all patient information and doses administered. Image quality 
will be assessed using the following scoring system: 0 = inadequate (grainy 
images with poor delineation of lesions); 1 = questionable (clear images, 
but lesion delineation is suboptimal and small lesions [1 cm] are hard to 
assess); 2 = acceptable (clear images, large and small lesion delineation is 
possible). Cohort scores will be calculated by adding the average patient 
image scores in each dosing group.  
In addition, the blinded readers will record lesion signal-to-noise, 
Maximum Standard Uptake Value (SUVmax), lesion-contrast-to-noise and 
lesion-to-normal tissue values derived from VOI values as described in the 
Independent Reader Manual. The cohort scores and image quality 
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evaluations will be used in the determination of the injected dose value for 
the Phase 2 study. 
Safety Assessments: 
All patients will be followed for adverse events for 24 hours post-injection.  
Severity of adverse events will be assessed independently by the 
Investigators and graded using the National Cancer Institute Common 
Terminology Criteria for Adverse Events version 5.0, in which Grades 1, 
2, 3, 4, and 5 describe adverse events as mild, moderate, severe, or 
medically significant but not life-threatening, life-threatening, and death 
related to adverse event, respectively.  
Routine clinical chemistry, hematology, PSA, and urinalysis will be 
performed at 4 hours post-injection on all patients. If no clinically 
significant changes are noted, no additional follow-up will be performed. If 
significant findings are noted, they will be reassessed at 24 hours post-
injection and followed until values return to normal or baseline, or until the 
Investigator and Medical Monitor determine it is no longer necessary.  
A 12-lead ECG will be obtained at 30 minutes and 3.5 hours post-injection 
for all patients. If no clinically significant changes are noted, no additional 
follow-up will be performed. If significant findings are noted, the patient 
will be reassessed at 24 hours post-injection and followed until values 
return to normal or baseline, or until the Investigator and Medical Monitor 
determine it is no longer necessary.  
Vital signs including heart rate, blood pressure, and respiratory rate will be 
obtained at 5 minutes, 30 minutes, 1 hour and 4 hours post-injection on all 
patients. If no clinically significant changes are noted, no additional 
follow-up will be performed. If significant findings are noted, they will be 
reassessed at 24 hours post-injection. 
Follow-up: 
Patients will be seen 24 hours post-injection for assessment of adverse 
events, clinically significant lab or ECG values or clinically significant 
vital signs. Patients with clinically significant changes will be followed 
until such events resolve or as decided by the Investigator and Medical 
Monitor. 
 
Phase 2 Study 
Procedures 
A total of 26 patients will be included in the Phase 2 portion of the study.  
Screening:  
All patients will be screened to ensure they meet all inclusion and no 
exclusion criteria for enrollment in the study. Written informed consent 
will be obtained for all patients enrolled in the study. 
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Baseline Assessments:  
Routine clinical chemistry, hematology, and urinalysis will be obtained for 
all patients prior to dosing. PSA will also be obtained for all patients prior 
to dosing. 
Medical history and physical examination will be performed prior to 
dosing. This will include information on the history of the prostate cancer. 
Concomitant medication history will also be obtained. 
Imaging Procedure: 
All patients will undergo PET/CT imaging at 1 hour ± 15 minutes and 4 
hours ± 30 minutes following copper Cu 64 PSMA I&T injection using the 
dose determined in Phase 1. The 1 hour and 4-hour images will be 
independently read by three experienced blinded readers for the detection 
of prostate cancer. Specifically, each reader will categorize images as 
“Disease” or “No Disease” based only on tumor uptake of copper Cu 64 
PSMA-I&T in each of the four regions: 1) prostate bed or prostate gland, 
2) lymph nodes (pelvic and extra pelvic), 3) bone, and 4) viscera/soft 
tissue.  
Efficacy Analysis: 
Composite Reference Standard 
All patients will undergo an efficacy assessment based on copper Cu 64 
PSMA I&T PET/CT results and the results of clinical presentation for 
evaluation against the Composite Reference Standard.  
The Composite Reference Standard is defined as follows:  
 
Local histopathology obtained from prostate cancer surgery or 
biopsy obtained within 60 days before or following copper Cu 64 PSMA 
I&T PET/CT, or 
 
If histopathology is not available, anatomical correlation of 
conventional image findings (e.g., targeted MRI or CT or any FDA-
approved PET PSMA agent) that are acquired prior to locoregional or 
systemic treatment and within 60 days before or following copper Cu 64 
PSMA I&T PET/CT 
Safety Assessments: 
All patients will be followed for adverse events for 24 hours post-injection. 
Severity of adverse events will be assessed independently by the 
Investigators and graded using the National Cancer Institute Common 
Terminology Criteria for Adverse Events version 5.0, in which Grades 1, 
2, 3, 4, and 5 describe adverse events as mild, moderate, severe or 
medically significant but not life-threatening, life-threatening, and death 
related to the adverse event, respectively.  
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To determine the region-level correct localization rate (CLR) of 
copper Cu 64 PSMA I&T injection PET/CT imaging for the detection of 
recurrent metastatic prostate cancer at 1- and 4-hours post-injection. The 
CLR is defined as the percentage of regions containing at least one true 
PET positive lesion, with exactly localized correspondence between 
PET/CT imaging and the Composite Reference Standard regardless of any 
co-existent false positive findings, within the same region, out of all 
regions containing at least one PET positive finding. 
 
To determine the patient-level correct detection rate (CDR) of 
copper Cu 64 PSMA I&T injection PET/CT imaging for the detection of 
recurrent metastatic prostate cancer at 1 hour and 4 hours post-injection. 
The CDR is defined as the percentage of patients who have a least one true 
PET positive lesion with exactly localized correspondence between PET 
imaging and the Composite Reference Standard regardless of any co-
existent false positive findings, out of all patients who are scanned  
Since all patients enrolled in the study will have disease, the CLR is a 
measure of the sensitivity of the copper Cu 64 PSMA I&T injection scan. 
Current methods have a CLR of 60%; thus, the hypothesis to be tested in 
the Phase 2 portion of the study is: H0: πC = π0 versus HA: πC > π0 where 
πC is the CLR for copper Cu 64 PSMA I&T injection and π0 is the CLR 
from the literature (estimated to be 60%). 
This hypothesis will be tested using an exact one-sample binomial test with 
a one-sided α=0.025. 
Secondary Objective: 
The secondary objective for the Phase 2 study is to compare the diagnostic 
quality of PET/CT images obtained at 1 hour and 4 hours post copper Cu 
64 PSMA I&T injection. 
Safety Endpoint: 
To assess the safety of copper Cu 64 PSMA I&T injection in patients with 
recurrent prostate cancer. Safety will be assessed by monitoring adverse 
events, clinical chemistry, hematology, urinalysis, ECG, and vital signs. 
Analysis Populations: 
Several analysis populations of patients are defined, which may provide a 
more complete description of the collected data, provide a logical 
mechanism for grouping and listing results based on an applied analysis, 
and/or allow appropriate stratification of various analyses.  
 
The Enrolled Patient Population (EPP) represents patients who sign 
an Informed Consent Form and have baseline data.  
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The Intent-to-Evaluate (ITE) Population are patients in the Enrolled 
Patient Population who satisfy the eligibility criteria and who have 
undergone a copper Cu 64 PSMA I&T imaging study.  
 
The Imaging Evaluable (IME) Population are patients in the ITE 
Population who have completed imaging procedures according to the 
protocol with technically satisfactory results. 
 
The Safety Population are patients who are administered copper Cu 
64 PSMA I&T injection.  
 
 
 
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