FAPI-CUP- Evaluating FAPI as a Novel Radiopharmaceutical for Cancer of Unknown Primary (FAPI-CUP)

FAPI-CUP - Evaluating FAPI as a Novel Radiopharmaceutical Targeting Cancer-associated Fibroblasts for the Diagnosis of Patients With Cancer of Unknown Primary

This is a prospective single arm cohort study designed to evaluate the diagnostic ability of 68Ga-FAPI-PET/CT scan in determining likely tissue of origin in Cancer of Unknown Primary (CUP) patients not identified by standard of care. Patients with CUP will be either treatment naïve or starting second-line treatment.

Study Overview

• Status: Recruiting
• Conditions: Cancer of Unknown Primary Site
• Intervention / Treatment: Drug: 68Ga-FAPi-46; Procedure: PET/CT imaging

Detailed Description

Cancers of unknown primary (CUP) account for 3-5% of all malignancies. The prognosis of patients diagnosed with CUP is poor, with a median overall survival of 9-12 months. Despite improvements in conventional diagnostic processes, the tissue of origin (ToO) is identified in <30% of CUP patients. PET/CT is increasingly used to determine the ToO, with the most commonly used PET radiotracer being the glucose analogue fluorine-18 fluorodeoxyglucose (FDG). Although PET/CT can change CUP patient management and identify primary sites, FDG has limited sensitivity for detecting some cancers, such as CUP. It has been reported that fibroblast activation protein (FAP) is highly expressed in some tumours, including CUP. 68Ga-FAPI (experimental drug) is a radiotracer that can specifically bind to FAP, and may enable the primary cancer site to be viewed using PET imaging. It is hypothesised that the use of 68Ga-FAPI-PET/CT will increase likely ToO diagnosis from 30% with current standard of care to 60%.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Linda Mileshkin; Phone Number: +61 3 85595000; Email: NMResearch@petermac.org
• Study Contact Backup: Name: Research Manager; Email: NMResearch@petermac.org

Study Locations

• Australia
  • Victoria
    • Bendigo, Victoria, Australia, 3550
      • Recruiting
      • Bendigo Health
      • Contact: Mark Warren; Phone Number: +61 3 5454 7210; Email: cancerresearch@bendigohealth.org.au
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter Maccallum Cancer Centre
      • Contact: Linda Mileshkin; Email: NMResearch@petermac.org
    • Warrnambool, Victoria, Australia, 3280
      • Not yet recruiting
      • South West Healthcare
      • Contact: Ian Collins; Email: swhct@swh.net.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participant has provided written informed consent
2. Participants aged 18 years or over at screening
3. Diagnosed with CUP based on a diagnostic work-up, including, but not limited to; a detailed clinical assessment; a CT scan of the chest/abdomen, and pelvis; pathological review of tumour tissue; and other appropriate tests as per the Cancer Council Optimal Care Pathway guidelines
4. Has not commenced current line of systemic treatment
5. Eastern Cooperative Oncology Group performance status 0 - 2
6. Life expectancy greater than 3 months

7. Adequate hematologic and organ function to commence systemic treatment, defined by the following laboratory results:

   1. Haemoglobin ≥ 90g/L
   2. Absolute neutrophil count ≥1.5 x 109/L
   3. Platelet count ≥ 100 x 109/L
   4. Creatinine clearance ≥ 30mL/min
   5. Serum bilirubin ≤ 1.5 x upper limit of normal (ULN); patients with known Gilbert's disease may have a bilirubin ≥ 3.0 x ULN
   6. Aspartate transaminase (AST) or alanine transaminase (ALT) ≤2 x ULN (or ≤ 5 x ULN in the presence of liver metastases)
8. Willing and able to comply with all study requirements, including all treatment and required assessments including follow-up procedures, in the investigator's judgment

Exclusion Criteria:

1. Uncontrolled medical or psychological conditions that may prevent commencement of systemic treatment.

2. Major surgical procedure within 6 weeks prior to study registration or active infection requiring systemic treatment

   a. Placement of vascular access devices is not considered major surgery.

3. Concurrent illness, including severe infection that may jeopardise the ability of the participant to undergo procedures outlined in this protocol with reasonable safety

4. Prior cancer diagnosis with the exception of:

   1. Malignancy treated with curative intent and with no known active disease ≥ 3years and of low potential risk of recurrence
   2. Adequately treated basal cell or squamous cell skin carcinoma or non-invasive melanoma
   3. Adequately treated non-muscle invasive bladder cancer (Tis, Ta and low grade T1 tumours)
   4. Adequately treated carcinoma in situ without evidence of disease
   5. Cancer subjects with incidental histologic findings of prostate cancer that, in the opinion of the Investigator, is not deemed to require active therapy (e.g., incidental prostate cancer identified following cystoprostatectomy that is tumour/node/metastasis stage ≤ pT2N0)
5. Greater than one prior line of systemic treatment
6. Known allergy or reaction to 18F or 68Ga tracer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 68Ga-FAPI-PET/CT; Patients receive 68Ga-FAPI IV then undergo PET/CT.	Drug: 68Ga-FAPi-46; FAPI-46 is a small molecular radiopharmaceutical that binds to the fibroblast activated protein on cancer associated fibroblasts. Gallium-68 (68Ga) is a positron-emitting isotope with a half-life of 68 minutes.; Procedure: PET/CT imaging; PET with the investigational tracer 68Ga-FAPI-46 with accompanying low-dose CT for anatomical localisation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients in which a likely tissue of origin is identified using 68Ga-FAPI-PET/CT	The proportion of patients in which 68Ga-FAPI-PET/CT identifies a likely Tissue of Origin (ToO) beyond that identified by standard of care (SoC) testing.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Standard Uptake Value measured on 68Ga-FAPI-PET/CT	The average SUVmax of the 5 most intense lesions measured on 68Ga-FAPI-PET/CT based on the best overall response rate assessed via RECIST after commencement of systemic therapy.	12 months
The proportion of patients in which the choice of treatment is changed after the 68Ga-FAPI-PET/CT	The change in patient management/treatment pre- and post- 68Ga-FAPI-PET/CT.	12 months

Collaborators and Investigators

• Sponsor: Peter MacCallum Cancer Centre, Australia

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2022
• Primary Completion (Anticipated): February 22, 2024
• Study Completion (Anticipated): February 22, 2024

Study Registration Dates

• First Submitted: February 15, 2022
• First Submitted That Met QC Criteria: February 28, 2022
• First Posted (Actual): March 3, 2022

Study Record Updates

• Last Update Posted (Actual): March 31, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: PET/CT; CUP; FAPI; FAPI-46
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Neoplasms, Unknown Primary; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; FAPI-46
• Other Study ID Numbers: PMC71838

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No