FAP, PDAC - Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
Fibroblast Activation Protein Inhibitor (FAPI), PDAC
Brief summary
This is a prospective, multi-center, single arm, open label, non-randomized study to evaluate the ability of \[68Ga\]FAPI-46 to detect FAP expressing cells in patients with resectable or borderline resectable PDAC. The \[68Ga\]FAPI-46 PET scans will be acquired after initial staging using institutional standard methods. If the participant is prescribed neoadjuvant therapy, a second \[68Ga\]FAPI-46 PET scan will be performed within 21 days prior to planned surgical resection. This will be followed by histopathology and IHC analyses and comparison to resected PDAC tumor specimens.
Interventions
DRUG[68Ga]FAPI-46
\[68Ga\]-FAPI-46 is a radioactive diagnostic agent indicated for use with Positron Emission Tomography (PET) imaging for the detection of Fibroblast Activation Protein (FAP) positive cancer cells and cancer-associated fibroblasts (CAF) in patients with pancreatic ductal adenocarcinoma (PDAC).
Sponsors
SOFIE
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Pathologically confirmed pancreatic ductal adenocarcinoma 2. Treatment-naïve 3. Staged as resectable or borderline-resectable 4. Planned to undergo surgical resection or to receive neoadjuvant therapy (i.e., chemotherapy, radiation therapy, or combination) and subsequent possible surgical resection 5. Anatomic imaging (e.g., CT, MRI) obtained within ≤ 28 days of consent 6. Age ≥ 18 years 7. Completed informed consent as determined per the IRB of record
Exclusion criteria
1. Pregnant as determined by a pregnancy test as per institutional guidelines for individuals of child-bearing potential 2. Declining to use effective contraceptive methods during the study (for individuals of child-producing potential) 3. Need for emergent surgery that would be delayed by participation 4. Bacterial, viral, or fungal infections requiring systemic therapy 5. Serious co-morbidities and serious nonmalignant disease (e.g., hydronephrosis, kidney failure, liver failure, systemic or local inflammatory or autoimmune diseases or other conditions) that in the opinion of the investigator, physician of record and/or Sofie could compromise patient safety and/or protocol objectives. 6. Known diagnosis of autoimmune disorders 7. Patients receiving any other investigational agent within the past 28 days 8. Breastfeeding. Note: nursing parents are allowed if the potential participant commits to pumping breast milk and discarding it from injection to ≥ 24 hours from the time of the \[68Ga\]FAPI-46 injection. 9. Known hypersensitivity to any excipients used in \[68Ga\]FAPI-46: trace amounts of sodium acetate sodium ascorbate and/or hydrochloric acid
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity of [68Ga]FAPI-46 PET Imaging to Detect PDAC, Using Histopathology as Truth Standard | Day 1 | Sensitivity was defined as the proportion of participants with histopathology-confirmed PDAC who had a positive \[⁶⁸Ga\]FAPI-46 PET result for the primary lesion. Sensitivity was calculated by comparing positive and negative \[⁶⁸Ga\]FAPI-46 PET findings with the corresponding histopathology results, using a single readable PET image matched to its reference histopathology assessment. Sensitivity was calculated as A / (A + C), where A represents true-positive findings and C represents false-negative findings. Higher sensitivity indicates a greater ability of \[⁶⁸Ga\]FAPI-46 PET to detect FAP-expressing disease and a lower likelihood of false-negative results, thereby reflecting the effectiveness of the imaging modality relative to the histopathological reference standard. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between [⁶⁸Ga]FAPI-46 PET Uptake (SUVmax) and IHC Staining Intensity (H-score) in FAP-positive Lesions | Day 1 | The association between \[⁶⁸Ga\]FAPI-46 PET uptake, measured by maximum standardized uptake value (SUVmax), and FAP expression, assessed by H-score from histopathology, was evaluated. The relationship between SUVmax and H-score was assessed using the Spearman rank correlation coefficient, with corresponding 95% confidence intervals, in participants with evaluable PET imaging and histopathology results may not be linear owing in part to the H score ceiling of 300. All available paired PET and H-score measurements were included; when both pre- and post-neoadjuvant therapy data were available, each time point was analyzed separately. Spearman's rho was selected because it assesses monotonic relationships between ordinal or continuous variables and does not assume linearity, which may not be appropriate for the relationship between SUVmax and H-score. |
| Sensitivity of [68Ga]FAPI-46 PET to Detect FAP-expressing Cells Using H-score as Standard of Truth | Day 1 | Sensitivity was defined as the proportion of participants with IHC confirmed FAP-expressing cells who had a positive \[68Ga\]FAPI-46 PET result for the primary lesion. Sensitivity was calculated as A / (A + C), where A represents true positive findings and C represents false negative findings. Higher sensitivity indicates a greater ability of \[68Ga\]FAPI-46 PET to detect IHC confirmed FAP expression and a lower likelihood of false negative results, thereby reflecting the effectiveness of the imaging modality relative to the IHC reference standard. Sensitivity was presented considering IHC-positive results using 3 IHC cut-off values: \> 50: Overall positive versus negative expression; \> 100: Moderate to high expression and \> 200: High expression only. |
| Specificity of [68Ga]FAPI-46 PET to Detect FAP-expressing Cells Using H-score as Standard of Truth | Day 1 | Specificity was defined as the proportion of participants without IHC-confirmed FAP-expressing cells who had a negative \[68Ga\]FAPI-46 PET result for the primary lesion. Specificity was calculated by comparing positive and negative \[68Ga\]FAPI-46 PET findings with the corresponding IHC results, using a single readable PET image matched to its reference IHC assessment. Specificity was calculated as D / (B + D), where B represents false-positive findings and D represents true-negative findings. PET results were compared with the corresponding IHC reference assessment using a single readable PET image per participant. Specificity was evaluated considering IHC-positive results using 3 IHC cut-off values \> 50: Overall positive versus negative expression; \> 100: Moderate to high expression and \> 200: High expression only. |
| Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Up to 2 years | An AE is any untoward medical occurrence in a clinical study participant whether or not considered related to the study intervention. A TEAE is any AE that occurs after receipt of one or more doses of study drug through the end of study for that participant. A SAE is defined as any untoward medical occurrence that, at any dose: results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent disability/incapacity or is a congenital anomaly/birth defect or is a medically significant / important event or reaction. |
Countries
United States
Participant flow
Recruitment details
This was a prospective, multicenter, single arm, open label, non-randomized study to evaluate the ability of \[68Ga\]FAPI-46 to detect fibroblast activation protein (FAP) expressing cells in participants with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC).
Pre-assignment details
A total of 63 participants were enrolled in the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 69.0 Years STANDARD_DEVIATION 8.96 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 15 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 63 |
| other Total, other adverse events | 3 / 58 |
| serious Total, serious adverse events | 1 / 58 |
Outcome results
None listed