Prostate Cancer
Conditions
Keywords
PET/CT, Imaging, Nuclear Medicine
Brief summary
The present study is a phase II, open label, single-center, non-randomized, single-dose study. Twenty subjects in total will be enrolled at Weill Cornell Medical College (WCMC)/ NYPH. The primary objective is to evaluate the ability of 89Zr-Df-IAB2M to detect localized, clinically significant (defined as: ≥ 0.5 cm3 with Gleason pattern ≥ 4) prostate cancer (PCa). After the screening period (up to 28 days), each subject will be scheduled to receive 10 mg infusion of IAB2M conjugated with 2.5 mCi 89Zr-Df. 2 - 4 days post-infusion, subjects will undergo a 89Zr-Df-IAB2M PET/CT scan. Images read by a Nuc Med MD reporting: location, SUV and, if possible, size of all areas with abnormal uptake. (they will also undergo a pelvic MRI if they have not obtained an MR image during the screening period or on day of infusion) Optional but recommended 68Ga-PSMA-HBED-CC (5±2mCi) injection and PET/CT scan (1 to 3 hours after the injection) will also be performed prior to radical prostatectomy depending on subject's availability and compliance. Patient will undergo radical prostatectomy after completion of above imaging procedures.
Detailed description
The primary endpoint of this study is the proportion of subjects with PSMA-positive (identified by H&E staining and immunohistochemistry) dominant PC lesion(s) greater than 5mm in diameter, whose lesion(s) have been successfully identified by 89Zr-Df-IAB2M imaging. Because this is an exploratory pilot study, no formal sample size/power calculation is required. However, with a sample size of 20 patients in the study, a two-sided 95% confidence interval for the proportion of patients successfully imaged by 89Zr-Df-IAB2M can be constructed to be within ± 19.0% of the observed proportion of patients with successful imaging by 89Zr-Df-IAB2M. This calculation assumes an 89Zr-Df-IAB2M imaging-success proportion of 75%. All estimates from the study will serve as preliminary data (i.e., hypothesis-generating) for future studies.
Interventions
DRUG89ZR-DF-IAB2M
injection of 10 milligrams of radioactive 89Zr-Df-IAB2M followed by PET/CT scan
Optional but recommended 68Ga-PSMA-HBED-CC (5±2mCi) injection and PET/CT scan (1 to 3 hours after the injection) will also be performed prior to radical prostatectomy depending on subject's availability and compliance.
Sponsors
Weill Medical College of Cornell University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically or cytologically confirmed localized prostate cancer that are scheduled to undergo radical prostatectomy. * Age \>18 years. * Patients must have laboratory values consistent with eligibility to undergo a radical prostatectomy: * creatinine less than or equal to 1.5 X upper limit of normal * creatinine clearance \> 60 mL/min * The effects of 89Zr-Df-IAB2M on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while her male partner is participating in this study, she should inform her treating physician immediately. * Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* Treatment or plans for treatment with radiation therapy, surgery, chemotherapy, or investigational therapy between the time of conventional imaging, 89Zr-Df-IAB2M PET/CT and the surgical resection used for the study evaluation. * Transrectal prostate biopsy performed less than four weeks prior to 89Zr-Df-IAB2M administration. * Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Subjects With PSMA-positive (Prostate-specific Membrane Antigen) Dominant PC Lesion(s) Greater Than 5mm in Diameter, Whose Lesion(s) Have Been Successfully Identified by 89Zr-df-IAB2M PET/CT | Up to 30 days pre-prostatectomy | The number of subjects whose lesions have been successfully identified through 89Zr-df-IAB2M PET/CT will be ascertained using a combination of the descriptive statistics and lesion-based analysis, which both utilize multiple measurements |
| The Number of Subjects With PSMA-positive Dominant PC Lesion(s) Greater Than 5mm in Diameter, Whose Lesion(s) Have Been Successfully Identified by 68Ga-PSMA-HBED-CC PET/CT | Up to 30 days pre-prostatectomy | The number of subjects with PSMA-positive (prostate-specific membrane antigen) dominant PC lesion(s) greater than 5mm in diameter, whose lesion(s) have been successfully identified by 68Ga-PSMA-HBED-CC PET/CT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Clinically Significant Lesions Detected by mpMRI | Up to 30 days pre-prostatectomy | pre-prostatectomy standard of care mpMRI used to determine the number of clinically significant lesions |
| The Number of Clinically Significant Lesions Detected by mpMRI in the Subset of Subjects Who Underwent 68Ga-PSMA-HBED-CC PET/CT | Up to 30 days pre-prostatectomy | The Number of Clinically Significant Lesions Detected by mpMRI in subjects who underwent 68Ga-PSMA-HBED-CC injection and PET/CT |
| The Number of Clinically Significant Lesions Detected by 89Zr-df-IAB2M PET/CT in the Subset of Subjects Who Underwent 68Ga-PSMA-HBED-CC PET/CT | Up to 30 days pre-prostatectomy | The Number of clinically significant lesions detected by 89Zr-df-IAB2M PET/CT in the subset of subjects who underwent 68Ga-PSMA-HBED-CC Injection and PET/CT |
| The Number of Lesions Involved in Extra-prostatic Extension Identified Through in Vivo 89Zr-df-IAB2M PET/CT | Up to 30 days pre-prostatectomy | — |
| The Number of Clinically-significant Lesions Detected by 89Zr-df-IAb2M PET/CT | Up to 30 days pre-prostatectomy | — |
| The Number of Occult Lymph Nodes Identified by in Vivo 89Zr-df-IAB2M PET/CT | Up to 30 days pre-prostatectomy | — |
| The Number of Occult Lymph Nodes Identified by in Vivo 68Ga-PSMA-11 PET/CT | Up to 30 days pre-prostatectomy | — |
| The Number of Observed or Reported Treatment-Emergent Adverse Events Following 89ZR-DF-IAB2M PET/CT (Positron Emission Tomography-Computed Tomography) | Up to 30 days pre-prostatectomy | All AEs, including unrelated AEs, expected, and unexpected AEs were included in the counts of adverse events |
| The Number of Observed or Reported Treatment-Emergent Adverse Events Following 68Ga-PSMA-HBED-CC PET/CT | Up to 30 days pre-prostatectomy | All AEs, including unrelated AEs, expected, and unexpected AEs were included in the counts of adverse events |
| The Number of Lesions Involved in Extra-prostatic Extension Identified Through 68Ga-PSMA-HBED-CC PET/CT | Up to 30 days pre-prostatectomy | — |
| The Number of Clinically Significant Lesions Detected by 68Ga-PSMA-HBED-CC PET/CT | Up to 30 days pre-prostatectomy | Participants underwent 68Ga-PSMA-HBED-CC injection and PET/CT scan (1 to 3 hours after the injection),e performed prior to radical prostatectomy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Interventional Injection of study drug followed by PET/CT imaging.
Optional but recommended 68Ga-PSMA-HBED-CC (5±2mCi) injection and PET/CT scan (1 to 3 hours after the injection) will also be performed prior to radical prostatectomy depending on subject's availability and compliance.
Followed by prostatectomy
89ZR-DF-IAB2M: injection of 10 milligrams of radioactive 89Zr-Df-IAB2M followed by PET/CT scan
68Ga-PSMA-HBED-CC: Optional but recommended 68Ga-PSMA-HBED-CC (5±2mCi) injection and PET/CT scan (1 to 3 hours after the injection) will also be performed prior to radical prostatectomy depending on subject's availability and compliance. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Interventional | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 5 Participants | — |
| Age, Categorical Between 18 and 65 years | 15 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 20 participants | — |
| Sex: Female, Male Female | 0 Participants | — |
| Sex: Female, Male Male | 20 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 9 |
| other Total, other adverse events | 0 / 20 | 0 / 9 |
| serious Total, serious adverse events | 0 / 20 | 0 / 9 |
Outcome results
Primary
The Number of Subjects With PSMA-positive Dominant PC Lesion(s) Greater Than 5mm in Diameter, Whose Lesion(s) Have Been Successfully Identified by 68Ga-PSMA-HBED-CC PET/CT
The number of subjects with PSMA-positive (prostate-specific membrane antigen) dominant PC lesion(s) greater than 5mm in diameter, whose lesion(s) have been successfully identified by 68Ga-PSMA-HBED-CC PET/CT
Time frame: Up to 30 days pre-prostatectomy
Population: 9 of the 20 enrolled subjects were analyzed, as only 9 subjects completed 68Ga-PSMA-HBED-CC PET/CT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 89Zr-Df-IAB2M, mpMRI, Prostatectomy | The Number of Subjects With PSMA-positive Dominant PC Lesion(s) Greater Than 5mm in Diameter, Whose Lesion(s) Have Been Successfully Identified by 68Ga-PSMA-HBED-CC PET/CT | 9 Participants |
Comparison: Clopper-Pearson (Exact) 95% confidence interval to assess precision of finding.95% CI: [0.66, 1]
Primary
The Number of Subjects With PSMA-positive (Prostate-specific Membrane Antigen) Dominant PC Lesion(s) Greater Than 5mm in Diameter, Whose Lesion(s) Have Been Successfully Identified by 89Zr-df-IAB2M PET/CT
The number of subjects whose lesions have been successfully identified through 89Zr-df-IAB2M PET/CT will be ascertained using a combination of the descriptive statistics and lesion-based analysis, which both utilize multiple measurements
Time frame: Up to 30 days pre-prostatectomy
Population: 19 of the 20 enrolled subjects were analyzed, as one of the 20 did not follow through with prostatectomy following 89Zr-df-IAB2M PET/CT, thus pathology is not available for 1 subject for this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 89Zr-Df-IAB2M, mpMRI, Prostatectomy | The Number of Subjects With PSMA-positive (Prostate-specific Membrane Antigen) Dominant PC Lesion(s) Greater Than 5mm in Diameter, Whose Lesion(s) Have Been Successfully Identified by 89Zr-df-IAB2M PET/CT | 18 Participants |
Comparison: Clopper-Pearson (Exact) 95% confidence interval to assess precision of finding.95% CI: [0.74, 0.99]
Secondary
The Number of Clinically Significant Lesions Detected by 68Ga-PSMA-HBED-CC PET/CT
Participants underwent 68Ga-PSMA-HBED-CC injection and PET/CT scan (1 to 3 hours after the injection),e performed prior to radical prostatectomy.
Time frame: Up to 30 days pre-prostatectomy
Population: 9 of the 20 enrolled subjects were analyzed, as only 9 subjects completed 68Ga-PSMA-HBED-CC PET/CT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 89Zr-Df-IAB2M, mpMRI, Prostatectomy | The Number of Clinically Significant Lesions Detected by 68Ga-PSMA-HBED-CC PET/CT | 10 Lesions |
Secondary
The Number of Clinically-significant Lesions Detected by 89Zr-df-IAb2M PET/CT
Time frame: Up to 30 days pre-prostatectomy
Population: 19 of the 20 enrolled subjects were analyzed, as one of the 20 did not follow through with prostatectomy following study 89Zr-df-IAB2M PET/CT, thus pathology is not available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 89Zr-Df-IAB2M, mpMRI, Prostatectomy | The Number of Clinically-significant Lesions Detected by 89Zr-df-IAb2M PET/CT | 22 Lesions |
Secondary
The Number of Clinically Significant Lesions Detected by 89Zr-df-IAB2M PET/CT in the Subset of Subjects Who Underwent 68Ga-PSMA-HBED-CC PET/CT
The Number of clinically significant lesions detected by 89Zr-df-IAB2M PET/CT in the subset of subjects who underwent 68Ga-PSMA-HBED-CC Injection and PET/CT
Time frame: Up to 30 days pre-prostatectomy
Population: 9 of the 20 enrolled subjects were analyzed, as only 9 subjects completed 68Ga-PSMA-HBED-CC PET/CT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 89Zr-Df-IAB2M, mpMRI, Prostatectomy | The Number of Clinically Significant Lesions Detected by 89Zr-df-IAB2M PET/CT in the Subset of Subjects Who Underwent 68Ga-PSMA-HBED-CC PET/CT | 9 Lesions |
Secondary
The Number of Clinically Significant Lesions Detected by mpMRI
pre-prostatectomy standard of care mpMRI used to determine the number of clinically significant lesions
Time frame: Up to 30 days pre-prostatectomy
Population: 19 of the 20 enrolled subjects were analyzed, as one of the 20 did not follow through with prostatectomy following study 89Zr-df-IAB2M PET/CT, thus pathology is not available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 89Zr-Df-IAB2M, mpMRI, Prostatectomy | The Number of Clinically Significant Lesions Detected by mpMRI | 18 Lesions |
Secondary
The Number of Clinically Significant Lesions Detected by mpMRI in the Subset of Subjects Who Underwent 68Ga-PSMA-HBED-CC PET/CT
The Number of Clinically Significant Lesions Detected by mpMRI in subjects who underwent 68Ga-PSMA-HBED-CC injection and PET/CT
Time frame: Up to 30 days pre-prostatectomy
Population: 9 of the 20 enrolled subjects were analyzed, as only 9 subjects completed 68Ga-PSMA-HBED-CC PET/CT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 89Zr-Df-IAB2M, mpMRI, Prostatectomy | The Number of Clinically Significant Lesions Detected by mpMRI in the Subset of Subjects Who Underwent 68Ga-PSMA-HBED-CC PET/CT | 8 Lesions |
Secondary
The Number of Lesions Involved in Extra-prostatic Extension Identified Through 68Ga-PSMA-HBED-CC PET/CT
Time frame: Up to 30 days pre-prostatectomy
Population: A subset of 9 subjects were injected with 68Ga-PSMA-HBED-CC followed by PET/CT scan, prior to prostatectomy.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| 89Zr-Df-IAB2M, mpMRI, Prostatectomy | The Number of Lesions Involved in Extra-prostatic Extension Identified Through 68Ga-PSMA-HBED-CC PET/CT | 4 extra-prostatic lesions |
Secondary
The Number of Lesions Involved in Extra-prostatic Extension Identified Through in Vivo 89Zr-df-IAB2M PET/CT
Time frame: Up to 30 days pre-prostatectomy
Population: 20 Subjects were injected with 10 milligrams of radioactive 89Zr-Df-IAB2M followed by PET/CT scan. 19 of those 20 completed prostatectomy and have pathology available for analysis.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| 89Zr-Df-IAB2M, mpMRI, Prostatectomy | The Number of Lesions Involved in Extra-prostatic Extension Identified Through in Vivo 89Zr-df-IAB2M PET/CT | 9 extra-prostatic lesions |
Secondary
The Number of Observed or Reported Treatment-Emergent Adverse Events Following 68Ga-PSMA-HBED-CC PET/CT
All AEs, including unrelated AEs, expected, and unexpected AEs were included in the counts of adverse events
Time frame: Up to 30 days pre-prostatectomy
Population: AEs were assessed for all 9 subjects who completed PET/CT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 89Zr-Df-IAB2M, mpMRI, Prostatectomy | The Number of Observed or Reported Treatment-Emergent Adverse Events Following 68Ga-PSMA-HBED-CC PET/CT | 0 Adverse Events |
Secondary
The Number of Observed or Reported Treatment-Emergent Adverse Events Following 89ZR-DF-IAB2M PET/CT (Positron Emission Tomography-Computed Tomography)
All AEs, including unrelated AEs, expected, and unexpected AEs were included in the counts of adverse events
Time frame: Up to 30 days pre-prostatectomy
Population: AEs were assessed for all 20 subjects who completed 89ZR-DF-IAB2M PET/CT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 89Zr-Df-IAB2M, mpMRI, Prostatectomy | The Number of Observed or Reported Treatment-Emergent Adverse Events Following 89ZR-DF-IAB2M PET/CT (Positron Emission Tomography-Computed Tomography) | 0 Adverse Events |
Secondary
The Number of Occult Lymph Nodes Identified by in Vivo 68Ga-PSMA-11 PET/CT
Time frame: Up to 30 days pre-prostatectomy
Population: A subset of 9 of the 20 subjects were analyzed, as only 9 subjects completed 68Ga-PSMA-HBED-CC PET/CT. All 9 of those subjects had post-prostatectomy pathology for analysis.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| 89Zr-Df-IAB2M, mpMRI, Prostatectomy | The Number of Occult Lymph Nodes Identified by in Vivo 68Ga-PSMA-11 PET/CT | 2 Occult Lymph Nodes |
Secondary
The Number of Occult Lymph Nodes Identified by in Vivo 89Zr-df-IAB2M PET/CT
Time frame: Up to 30 days pre-prostatectomy
Population: 19 of the 20 enrolled subjects were analyzed, as one of the 20 did not follow through with prostatectomy following study 89Zr-df-IAB2M PET/CT, thus pathology is not available.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| 89Zr-Df-IAB2M, mpMRI, Prostatectomy | The Number of Occult Lymph Nodes Identified by in Vivo 89Zr-df-IAB2M PET/CT | 7 Occult Lymph Nodes |