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

Sponsor

Aalborg University Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05903807

Collaborator

(none)

Enrollment

Arm

136

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: 68Ga-FAPi-46	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Intervention Model Description:

Fifty consecutive patients newly diagnosed with ovarian cancer are recruitedFifty consecutive patients newly diagnosed with ovarian cancer are recruited

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Jan 1, 2035

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ovarian cancer or high risk of ovarian cancer 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 Ovarian cancer patients undergo 68Ga-FAPI-46 at primary staging and at restaging

Arm

Intervention/Treatment

Experimental: Ovarian cancer or high risk of ovarian cancer

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

Ovarian cancer patients undergo 68Ga-FAPI-46 at primary staging and at restaging

Outcome Measures

Primary Outcome Measures

Diagnostic accuracy [2 years]
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
Staging [2 years]
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.
Patient management [2 - 2.5 years]
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

Secondary Outcome Measures

Uptake values [2 years]
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)
Chemotherapy effect on uptake values [2 - 2.5 years]
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.
Unexpected 68Ga-FAPI-46 PET/CT findings [1-2 years]
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
Interobserver readability [4 years]
Conduct an interobserver study of FAPI PET/CTs performed in the present and other future FAPI PET/CT in cancers studies.
Prognostic value [10 years]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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).