Gynecologic Cancer
Conditions
Keywords
Uterine cancer, Ovarian cancer, Hysterectomy, Salpingo-oophorectomy
Brief summary
The goal of this research is to determine the accuracy of PSMA positron emission tomography (PET) and multi-parametric magnetic resonance (MR) imaging to detect the presence of gynecological cancer cells in the body.
Detailed description
The investigators will evaluate a novel second-generation low-molecular-weight prostate specific membrane antigen (PSMA)-based positron emission tomography (PET) agent, 18F-DCFPyL, to determine the presence or absence of cancer, the accurate distribution of cancer and the normal biodistribution of PSMA in the abdomen and pelvis on PET imaging. PSMA, also known as folate hydrolase 1 and glutamate carboxypeptidase II, is an enzyme associated with prostate cancer but has been also found to be expressed in the tumor neovasculature of many different types of non-prostate cancer tumors. PSMA-based 18F-DCFPyL PET demonstrates very high tumor-to-background ratio when studied in other tumors, including prostate tumors. MR imaging is a highly sensitive and specific imaging modality that can be used for gynecologic cancers. MR images can be obtained in conjunction with PSMA PET, adding additional anatomic and multi-parametric MRI information without the need for a second imaging appointment.
Interventions
DRUGPSMA-based 18F-DCFPyL PET tracer
PSMA-based 18F-DCFPyL PET tracer that will be used to determine the presence or absence of cancer
Sponsors
University of Wisconsin, Madison
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 99 Years
Healthy volunteers
Yes
Inclusion criteria
for healthy female controls N=12 (includes up to 6 Dosimetry participants): * Women with no suspected gynecological cancer. * No contraindications for MR or PET imaging. * Greater than or equal to 18 years of age. * Scheduled to undergo a hysterectomy and/or salpingo-oophorectomy Inclusion Criteria for female controls (Dosimetry): * Women with or without suspected gynecological cancer. * No contraindications for MR or PET imaging. * Greater than or equal to 18 years of age. Inclusion Criteria for gynecological cancer patients (N=40): * Women with known or suspected gynecological cancer * No contraindications for MR or PET imaging. * Greater than or equal to 18 years * Have had or are scheduled to undergo a hysterectomy and/or salpingo-oophorectomy
Exclusion criteria
* Women that are pregnant or breast-feeding. * Age \<18 * Inability to provide informed consent on their own behalf * Severe kidney dysfunction (GFR \<30 mL/min/1.73m2)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diagnostic Accuracy | up to 1 day | Estimate the frequency with which PSMA PET and MR imaging and final IHC staining disagree in their classifications of presence of disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biodistribution of PSMA Measured by SUVmax in Normal Tissue | up to 1 day | Record the normal biodistribution of PSMA as detected in normal tissue controls, by the resulting PET imaging. |
| Biodistribution of PSMA Measured by SUVmax in Cancer Tissue | up to 1 day | Record the biodistribution of PSMA as detected in cancer tissue, by the resulting PET imaging. |
| Radiodosimetry of PSMA | up to 1 day | The radiodosimetry of PSMA-based 18F-DCFPyL will be measured in normal female controls via the resulting PET images. |
| Sensitivity and Specificity of PSMA-based PET/MR | up to 1 day | Record the distribution of PSMA in cancer tissue. |
Countries
United States
Participant flow
Recruitment details
15 participants were consented from November 2017 to December 2019. Research was suspended in March 2020 per the COVID-19 pandemic. The study opened to enrollment again in June 2022; there were no more participants consented. The investigator terminated the study in January 2023 due to slow accrual of patients with ovarian cancer and due to lack of funding. No participants were enrolled in the Dosimetry group.
Participants by arm
| Arm | Count |
|---|---|
| Healthy Control Non-Dosimetry Group The control group will consists of women with no imaging evidence of gynecological cancer, who are undergoing hysterectomy and salpingo-oophorectomy. Women will receive PSMA-based 18F-DCFPyL tracer and PET/MR imaging. n=6
PSMA-based 18F-DCFPyL PET tracer: PSMA-based 18F-DCFPyL PET tracer that will be used to determine the presence or absence of cancer | 2 |
| Patient Group The patient group will consist of women with suspected gynecological cancers who are undergoing hysterectomy and salpingo-oophorectomy. Women will receive standard of care PSMA-based 18F-DCFPyL tracer and PET/MR imaging. n=40
PSMA-based 18F-DCFPyL PET tracer: PSMA-based 18F-DCFPyL PET tracer that will be used to determine the presence or absence of cancer | 12 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | no visible evidence of tumor on MRI | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Healthy Control Non-Dosimetry Group | Patient Group |
|---|---|---|---|
| Age, Continuous | 56.7 years | 53.5 years | 57.3 years |
| Race and Ethnicity Not Collected | 0 Participants | — | — |
| Region of Enrollment United States | 14 participants | 2 participants | 12 participants |
| Sex: Female, Male Female | 14 Participants | 2 Participants | 12 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Suspected Participant Diagnosis Cervical Cancer | 0 Participants | 0 Participants | 0 Participants |
| Suspected Participant Diagnosis Endometrial Cancer | 3 Participants | 0 Participants | 3 Participants |
| Suspected Participant Diagnosis Healthy Controls | 2 Participants | 2 Participants | 0 Participants |
| Suspected Participant Diagnosis Other Cancer | 1 Participants | 0 Participants | 1 Participants |
| Suspected Participant Diagnosis Ovarian Cancer | 8 Participants | 0 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 12 |
| other Total, other adverse events | 0 / 2 | 0 / 12 |
| serious Total, serious adverse events | 0 / 2 | 0 / 12 |
Outcome results
Primary
Diagnostic Accuracy
Estimate the frequency with which PSMA PET and MR imaging and final IHC staining disagree in their classifications of presence of disease.
Time frame: up to 1 day
Population: Calculating accuracy relies on the IHC staining as the gold standard. IHC staining was not done because the study was terminated due to low recruitment and loss of funds. Because the IHC staining was not performed, there is no gold standard by which to perform accuracy, sensitivity and specificity analysis.
Secondary
Biodistribution of PSMA Measured by SUVmax in Cancer Tissue
Record the biodistribution of PSMA as detected in cancer tissue, by the resulting PET imaging.
Time frame: up to 1 day
Population: This was performed on the Patient population. There was only one patient with confirmed ovarian cancer with PSMA uptake.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Patient Group | Biodistribution of PSMA Measured by SUVmax in Cancer Tissue | 10.5 SUVmax |
Secondary
Biodistribution of PSMA Measured by SUVmax in Normal Tissue
Record the normal biodistribution of PSMA as detected in normal tissue controls, by the resulting PET imaging.
Time frame: up to 1 day
Population: This was performed on the entire population of patients recruited in both the Healthy Control and Patient group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Control Non-Dosimetry Group | Biodistribution of PSMA Measured by SUVmax in Normal Tissue | Aorta at carina | 2.0 SUVmax | Standard Deviation 0.1 |
| Healthy Control Non-Dosimetry Group | Biodistribution of PSMA Measured by SUVmax in Normal Tissue | Liver - Right Lobe | 12.1 SUVmax | Standard Deviation 5.4 |
| Healthy Control Non-Dosimetry Group | Biodistribution of PSMA Measured by SUVmax in Normal Tissue | Myometrium | 2.2 SUVmax | Standard Deviation 0.4 |
| Healthy Control Non-Dosimetry Group | Biodistribution of PSMA Measured by SUVmax in Normal Tissue | Endometrium | 5.9 SUVmax | Standard Deviation 1.8 |
| Healthy Control Non-Dosimetry Group | Biodistribution of PSMA Measured by SUVmax in Normal Tissue | Cervix | 4.0 SUVmax | Standard Deviation 1.1 |
| Healthy Control Non-Dosimetry Group | Biodistribution of PSMA Measured by SUVmax in Normal Tissue | Right Ovary | 1.5 SUVmax | Standard Deviation 1.7 |
| Healthy Control Non-Dosimetry Group | Biodistribution of PSMA Measured by SUVmax in Normal Tissue | Corpus Luteum | 6.3 SUVmax | — |
| Healthy Control Non-Dosimetry Group | Biodistribution of PSMA Measured by SUVmax in Normal Tissue | Left Ovary | 1.7 SUVmax | Standard Deviation 1.4 |
| Patient Group | Biodistribution of PSMA Measured by SUVmax in Normal Tissue | Left Ovary | 2.3 SUVmax | Standard Deviation 0.5 |
| Patient Group | Biodistribution of PSMA Measured by SUVmax in Normal Tissue | Aorta at carina | 1.7 SUVmax | Standard Deviation 0.5 |
| Patient Group | Biodistribution of PSMA Measured by SUVmax in Normal Tissue | Cervix | 3.3 SUVmax | Standard Deviation 0.5 |
| Patient Group | Biodistribution of PSMA Measured by SUVmax in Normal Tissue | Liver - Right Lobe | 10.0 SUVmax | Standard Deviation 0.5 |
| Patient Group | Biodistribution of PSMA Measured by SUVmax in Normal Tissue | Corpus Luteum | 5.9 SUVmax | Standard Deviation 0.5 |
| Patient Group | Biodistribution of PSMA Measured by SUVmax in Normal Tissue | Myometrium | 2.9 SUVmax | Standard Deviation 0.5 |
| Patient Group | Biodistribution of PSMA Measured by SUVmax in Normal Tissue | Right Ovary | 3.0 SUVmax | Standard Deviation 0.5 |
| Patient Group | Biodistribution of PSMA Measured by SUVmax in Normal Tissue | Endometrium | 4.8 SUVmax | Standard Deviation 0.5 |
Secondary
Radiodosimetry of PSMA
The radiodosimetry of PSMA-based 18F-DCFPyL will be measured in normal female controls via the resulting PET images.
Time frame: up to 1 day
Population: No data was collected for this. There were no participants enrolled into the Dosimetry group. The study was terminated early due to low accrual and loss of funding.
Secondary
Sensitivity and Specificity of PSMA-based PET/MR
Record the distribution of PSMA in cancer tissue.
Time frame: up to 1 day
Population: Calculating sensitivity and specificity relies on the IHC staining as the gold standard. IHC staining was not done because the study was terminated due to low recruitment and loss of funds. Because the IHC staining was not performed, there is no gold standard by which to perform accuracy, sensitivity and specificity analysis.