(S)-2,2',2''-(10-(2-(4-(3-((4-(2-(2-CYANO-4,4-DIFLUOROPYRROLIDIN-1-YL)-2-OXOETHYLCARBAMOYL)-QUINOLIN-6-YL)(METHYL)AMINO)-PROPYL)PIPERAZIN-1-YL)-2-OXOETHYL)-68GA-[1,4,7,10]-TETRAAZACYCLODODECANE-1,4,7-TRIYL)TRIACETATE for Gastrointestinal cancers | Hepatocellular carcinoma | Cholangiocarcinoma | Gastric cancer | Pancreatic cancer | Colorectal cancer | Oesophageal cancer

Inclusion criteria

• {"criterion_text":"- Proven or suspected gastrointestinal cancers including: - Hepatocellular carcinoma - Cholangiocarcinoma - Gastric cancer - Pancreatic cancer - Colorectal cancer - Oesophageal cancer"}
• {"criterion_text":"- At initial staging or re-staging of disease"}
• {"criterion_text":"- At least one detectable tumour lesion with any diameter > 1cm"}
• {"criterion_text":"- Intended or performed surgery of biopsy of tumor within 8 weeks before or 8 weeks after enrollment and participants consent to utilise biopsy/tumour specimen for immunohistochemical analysis of FAP expression"}
• {"criterion_text":"- Age ≥ 18 years"}
• {"criterion_text":"- Participant Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2"}
• {"criterion_text":"- Women of child bearing potential (WOCBP), defines as all women physiologically capable of becoming pregnant, can only be included after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test within 24 hours before radiopharmaceutical application"}

Exclusion criteria

• {"criterion_text":"- Participant cannot give consent for the study"}
• {"criterion_text":"- Sexually active males must use a condom during intercourse during the interventional period. A condom is required to be used also by vasectomized men in order to prevent delivery of the study compound via seminal fluid"}
• {"criterion_text":"- QTcF >470 msec for females and QTcF >450 msec for males on screening ECG or history of congenital long QT syndrome"}
• {"criterion_text":"- Known or expected hypersensitivity to 68Ga-68-FAPI-46 or any of the relevant excipients"}
• {"criterion_text":"- Participant can not lie flat or tolerate 68Ga-FAPI-46 PET imaging"}
• {"criterion_text":"- Prior external beam radiation therapy (EBRT) within 1 month of enrolment to tumour lesions intended for surgery or biopsy"}
• {"criterion_text":"- Prior chemotherapy, immunotherapy, biologic or targeted oncologic therapy within 1 month prior 68Ga-FAPI-46 PET"}
• {"criterion_text":"- Unwillingness or inability to comply with study and follow-up procedures"}
• {"criterion_text":"- History of disease or condition that may critically interfere with participation in this study at the discretion of the investigators"}
• {"criterion_text":"- Pregnant, lactating, or breast-feeding women"}
• {"criterion_text":"- Women of child bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, are not allowed to participate in this study, unless they are using highly effective methods of contraception during the interventional period. Highly effective contraception methods include: • True sexual abstinence: defined as refraining from heterosexual intercourse, when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to IMP, and withdrawal are not acceptable methods of contraception.• Vasectomised partner is a highly effective birth control method if the partner is the sole sexual partner of the study participant and the vasectomised partner has received medical assessment of the surgical success. • Bilateral tubal occlusion. • Combined (oestrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: - oral - intravaginal - transdermal• Progestogen-only hormonal contraception associated with inhibition of ovulation: - oral - injectable - implantable • Placement of an intrauterine device or intrauterine hormone-releasing system"}
• {"criterion_text":"- Post-menopausal women are allowed to participate in this study. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms), or six months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels > 40mIU/mL or have had surgical bilateral oophorectomy or bilateral salpingectomy or hysterectomy or tubal ligation at least six weeks prior to screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential"}

Primary endpoints

• {"endpoint_text":"- Positive predictive value (PPV) on a per-region- and per-patient-basis of 68Ga-FAPI-46 PET for detection of gastrointestinal cancers, confirmed by histopathology/ biopsy (reached for ≥ 75%)","definition_or_measurement_approach":"PPV assessed on a per-region and per-patient basis for detection of gastrointestinal cancers, confirmation by histopathology/biopsy, target threshold ≥ 75%."}

Secondary endpoints

• {"endpoint_text":"- Sensitivity and specificity of 68Ga-FAPI-46 PET on a per-patient and per-region-basis for detection of gastrointestinal cancers confirmed by histopathology/ biopsy (separate for regional, extra-regional and distant locations)","definition_or_measurement_approach":"Sensitivity and specificity measured per-patient and per-region, confirmation by histopathology/biopsy; analyses stratified for regional, extra-regional and distant locations."}
• {"endpoint_text":"- Detection rate of 68Ga-FAPI-46 PET versus previous standard imaging on a per-patient and per-region basis for detection of tumour location, also stratified by tumour marker serum level","definition_or_measurement_approach":"Detection rate comparison between 68Ga-FAPI-46 PET and prior standard imaging per-patient and per-region; stratification by tumour marker serum levels."}
• {"endpoint_text":"- Sensitivity and specificity of 68Ga-FAPI-46 PET versus previous standard imaging on a per-patient and per-region-basis for detection of tumour lesions confirmed by combined histopathology/ biopsy/ follow-up imaging/ clinical follow-up reference standard (separate for regional, extra-regional and distant locations","definition_or_measurement_approach":"Sensitivity and specificity comparison versus prior standard imaging using combined reference standard (histopathology/biopsy/follow-up imaging/clinical follow-up); analyses per-patient and per-region and by location."}
• {"endpoint_text":"- Inter-reader reproducibility","definition_or_measurement_approach":"Assessment of reproducibility between readers interpreting 68Ga-FAPI-46 PET images (inter-reader agreement metrics)."}
• {"endpoint_text":"- Impact on therapy management will be evaluated by pre- & post-imaging questionnaires sent to the treating physicians","definition_or_measurement_approach":"Impact assessed using questionnaires completed by treating physicians before and after imaging to evaluate changes in treatment management."}
• {"endpoint_text":"- Change in staging/ prognostic groups","definition_or_measurement_approach":"Assessment of change in staging or prognostic grouping pre- and post-68Ga-FAPI-46 PET imaging."}
• {"endpoint_text":"- Association between 68Ga-FAPI-46 PET uptake intensity and histopathologic FAP expression","definition_or_measurement_approach":"Correlation analysis between PET uptake intensity and histopathologic FAP expression from biopsy specimens."}
• {"endpoint_text":"- Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) including vital signs and changes in laboratory parameters","definition_or_measurement_approach":"Safety assessed by recording AEs and SAEs, monitoring vital signs and laboratory parameter changes following single imaging dose."}

Germany

Earliest CTIS Part Ii Submission Date

10-02-2025

Latest Decision Or Authorization Date

13-03-2025

Processing Time Days

31

Number Of Sites

2

Number Of Participants

150

Primary sponsor

Full Name

Universitaetsklinikum Essen AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany