[18F]F-FAPI PET-CT to Identify Carcinoma of Unknown Primary Origin

Overview

The investigators will determine the proportion of CUP patients in whom the primary tumor can be identified by \[18F\]F-FAPI PET-CT.

Detailed description

Carcinoma of unknown primary origin (CUP) is a diverse group of cancers defined by the presence of metastatic disease with no identified primary tumor after exhaustive diagnostic work-up. Absence of a known targetable primary tumor precludes patients from receiving tumor-specific evidence-based therapies which significantly impacts the life expectancy of CUP patients. In this investigator-initiated and patient association-driven, multi-center, prospective clinical study we aim to detect the primary tumor by PET-CT using the novel radiotracer \[18F\]F-fluoro fibroblast activation protein inhibitor (F-FAPI). We will include 50 patients (aged \>18 year) who have been diagnosed with CUP after standard diagnostic work-up including FDG PET-CT. Participation in the study entails a one-time \[18F\]F-FAPI PET-CT examination in one of the six study centers (UMC Groningen, UMC Utrecht, Antoni van Leeuwenhoek, Radboudumc, Maastricht UMC, Erasmus MC). For the interpretation of images, central reading will be performed and results will be made available to the treating physician with an accompanying recommendation for additional diagnostics and/or treatment. After 6 months, the results of the \[18F\]F-FAPI PET-CT will be compared with patient follow up, including clinical, radiological and pathological outcome parameters. These findings will holistically be discussed in a multidisciplinary Truth Panel meeting to determine a uniform verdict with regard to the clinical value of \[18F\]F-FAPI for CUP. We hypothesize that \[18F\]F-FAPI PET-CT will detect the primary tumor in at least 15% of our CUP patients.¬

Interventions

• Diagnostic test [18F]F-FAPI PET-CT
  Each patient will receive a FAPI PET-CT.

Primary outcome measures

• Detection of the primary tumor by [18F]F-FAPI PET-CT [Time frame: 2 years]

Secondary outcome measures (1)

• Sensitivity, specificity, positive- and negative predictive value of [18F]F-FAPI PET-CT [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years old
• Histologically-confirmed metastatic disease without identification of a primary tumor after standard diagnostic work-up, according to the national care pathway for CUP (in Dutch: Regionaal Zorgpad Primaire Tumor Onbekend), which includes at least an \[18F\]FDG PET-CT.

Exclusion criteria

• Patients with metastasis from a known primary tumor.
• Sarcomas, melanomas, germ cell tumors, neuroendocrine tumors and haematological malignancies whose exact site of origin is not established.
• History of malignancy within 5 years prior to \[18F\]F-FAPI PET-CT scan, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma in-situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in-situ, or Stage I uterine cancer.
• Prior systemic therapy for the treatment of CUP.
• Radiotherapy prior to \[18F\]F-FAPI PET-CT. Off note: radiotherapy with palliative intent for symptomatic skeleton lesions is allowed.
• Impaired renal function, defined as eGFR (MDRD) <25 ml/min/1,73 m2. An exception can be made in consultation with the treating physician.
• WHO performance status >2 (Vademecum).
• Pregnancy/breastfeeding. For the latter, temporary discontinuation may be considered.
• Known allergic reaction to therapeutic radiopharmaceuticals
• Inability to lie still on the back for the duration of PET-CT
• Any (other) condition, disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that may affect the interpretation of the results, or which might contribute substantially to the patient's experience of study burden (such as non-suppressible claustrophobia)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

Netherlands · 6 centers

• Antoni van Leeuwenhoekziekenhuis — Amsterdam
• UMC Groningen — Groningen
• Maastricht UMC — Maastricht
• Radboud UMC — Nijmegen
• Erasmus Medical Center — Rotterdam
• UMC Utrecht — Utrecht

Identifiers

NCT: NCT06644716 · 2023-505592-69-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗