[68Ga]Ga-FAPI-46 PET/CT in Ovarian Cancer

Study Overview
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Brief Summary
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Fifty (n=50) patients with newly diagnosed ovarian cancer will undergo FAPI PET/CTs in addition to routine diagnostic workup (including FDG PET/CT) at primary staging and restaging. The FAPI PET/CT results will be compared to conventional imaging (including FDG PET/CT) using histopathology as reference standard, and the diagnostic accuracy will be determined. FAP-immunohistochemistry will be conducted in surgical specimens. FAPI PET/CT's impact on patient management and the prognostic value of FAPI PET/CT will be evaluated.

Detailed Description
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A new and promising PET-tracer in oncology has been developed; Gallium-68 labelled fibroblast activation protein inhibitor (FAPI). In general, FAPI PET/CT delivers increased sensitivity compared to 18F-Fluorodeoxyglucose (FDG) PET/CT in cancer types of mesenchymal origin (i.e., sarcomas), and in cancers characterized by a large proportion of stromal cells such as gastric and pancreatic cancers. It is currently debated whether FAPI PET/CT will take over FDG PET/CTs well-established role in oncological PET/CT, but more studies are needed to evaluate the diagnostic accuracy. The clinical interest in FAPI extends beyond the use as a diagnostic tool, as the 68Ga-isotope can be replaced by a β-emitting isotope, e.g., 177-Lu or 90-Y, enabling radionuclide therapy of FAPI-avid cancers. Not long after the development of FAPI, the clinical value of FAPI PET/CT in ovarian cancer patients was highlighted by several case reports where FAPI PET/CT detected far more peritoneal metastases than FDG PET/CT. Only recently have cohort studies in ovarian cancer been conducted. In these studies, FAPI PET/CT demonstrates promising results when compared to FDG PET/CT, especially in peritoneal lesions. Even though the results of FAPI PET/CT compared to conventional imaging seem convincing, there are several limitations and therefore FAPI PET/CT is not yet implemented in cancer diagnostics. The investigators are conducting a prospective explorative study complying with the Standard for Reporting Diagnostic Accuracy (STARD) criteria where 50 patients with ovarian cancer are recruited. Study subject will undergo FAPI PET/CT at primary staging (before treatment, i.e., neoadjuvant chemotherapy or surgery) and at restaging (after neoadjuvant chemotherapy - before surgery) in addition to routing diagnostic workup (including FDG PET/CT). The FAPI PET/CT will be blinded and the choice of treatment will not be influence by the FAPI PET/CT results'. The additional scans will not interfere with or delay routine diagnostic workup or treatment. The FAPI PET/CTs (at primary staging and restaging) will be compared to the corresponding FDG PET/CTs, and histopathology of biopsied material and surgical specimens will serve as reference standard. FAPI PET/CTs before and after neoadjuvant chemotherapy will be assessed and compared to the FDG PET/CTs. FAP-immunohistochemistry will be conducted in surgical specimens. A tentative retrospective Multi-Disciplinary Team conference (MDT) will be arranged where treating clinicans are presented the FAPI PET/CT, and potential changes in patient management will be evaluated. This tentative MDT will not influence patient management. Follow up will be conducted for 10 years to evaluate the prognostic value of FAPI PET/CT.

Official Title
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[68Ga]Ga-FAPI-46 PET/CT: The Diagnostic Accuracy for Primary Staging and Re-staging of Patients With Ovarian Cancer

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: 68Ga-FAPi-46


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed with biopsy verified ovarian cancer or highly suspected to have ovarian cancer (based on all data presented at the gynecological cancer MDT) and referred to primary staging with FDG PET/CT Deemed resectable and operable at the MDT with or without neoadjuvant chemotherapy Considered physically and mentally able to participate in the research project 18-years or older and able to consent to project participation Can read and understand Danish Exclusion Criteria: Patients with non-resectable, inoperable, or recurrent ovarian cancer Patients with an imminent need for surgery or in an emergency Known concurrent other malignancy within the previous 5 years other than non-melanoma skin cancer Patients not suited for surgery or neoadjuvant chemotherapy followed by surgery Subject weighing more than 180 kg (weight limit scanner) or unable to fit within the imaging gantry History of allergic reactions / hypersensitivity attributed to 18F-FDG or 68Ga-FAPI-46. Severe claustrophobia unresponsive to oral anxiolytics Subjects with any medical condition or other circumstances that, in the opinion of the Investigator, would significantly decrease the reliability of data, achievement of study objectives or completing the study. Pregnant, lactating, or breastfeeding women. Potential pregnant women of childbearing potential [1] not using effective contraceptives [2]. Potential pregnancy will be ascertained by a pregnancy test (urine humane choriogonadotropin (HCG)) or serum b-HCG within 48 hours prior to the FAPI PET/CT. Inability to remain still for the duration of the examination Women of childbearing potential are defined as all women physiologically capable of becoming pregnant, i.e., not sterilized (bilateral tubectomy/occlusion, hysterectomy, bilateral oophorectomy) and not post-menopausal. In cases of uncertain menopausal status, serum follicle stimulating hormone (FSH) levels and menstruation history can be assessed Effective contraceptives include sexual abstinence, vasectomized partner, combined hormonal contraception (oral, intravaginal, transdermal), progesterone-only contraceptive (oral, injectable, implantable), or working intrauterine device (hormonal, non-hormonal).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Fifty consecutive patients newly diagnosed with ovarian cancer are recruited
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ovarian cancer or high risk of ovarian cancer<br>Patients with newly diagnosed ovarian cancer or high risk of ovarian cancer undergo FAPI PET/CT in addition to conventional imaging | Drug: 68Ga-FAPi-46<br>* Ovarian cancer patients undergo 68Ga-FAPI-46 at primary staging and at restaging<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic accuracy | Diagnostic accuracy Compare the FAPI PET/CT and FDG PET/CT findings in primary tumor, regional lymph nodes and distant metastases to a histopathological reference standard where the sensitivity, specificity, positive predicative value, and negative predicative values of the PET/CTs are determined, both at primary staging and at restaging | 2 years | 
| Staging | Compare the cancer stage as determined by FAPI PET/CT compared to conventional imaging (including FDG PET/CT) at primary staging and at restaging (after neoadjuvant chemotherapy). The proportion of patients downstaged, unchanged stage, and upstaged, due to the added FAPI PET/ CT are determined. | 2 years | 
| Patient management | Investigate what proportion of patients will be (hypothetically) treated differently due to an added FAPI PET/CT at primary staging and at restaging (after neoadjuvant chemotherapy) by the treating clinicians | 2 - 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uptake values | Standardized uptake value (SUV) and tumor-to-background ratio (TBR) values for primary, regional lymph nodes, and distant metastases for FAPI PET/CT and compare these values to FDG PET/CT, both at primary staging and at restaging (after neoadjuvant chemotherapy) | 2 years | 
| Chemotherapy effect on uptake values | Changes in SUV and TBR in primary, regional lymph nodes, and distant metastases for FAPI PET/CT - from before to after neoadjuvant chemotherapy and compare these values to the FDG PET/CT parameters. | 2 - 2.5 years | 
| Unexpected 68Ga-FAPI-46 PET/CT findings | Seek supplementary information in medical records, biochemistry, pathology, or other imaging modalities for a final diagnosis/condition in cases of unexpected FAPI PET/CT findings not related to the known cancer | 1-2 years | 
| Interobserver readability | Conduct an interobserver study of FAPI PET/CTs performed in the present and other future FAPI PET/CT in cancers studies. | 4 years | 
| Prognostic value | Investigate the prognostic value of FAPI PET/CT versus FDG PET/CT by conducting a 10 years follow up on included cancer patients. Overall survival (OS) and Recurrence free survival (RFS) will be estimated | 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, FAPI, FAPI PET/CT, Fibroblast activation protein inhibitor, Ovarian cancer