Evaluation of 18F-Fluorodeoxyglucose PET/CT for Detecting Occult Malignancy in Patients Aged 50+ with Unprovoked Venous Thromboembolism

The primary objective of this study is to determine whether the addition of **FDG-PET/CT** to a limited screening strategy reduces the number of missed cancer diagnoses compared to a limited cancer screening strategy alone in patients aged 50 years or older with a first unprovoked venous thromboembolism (VTE) over a 1-year follow-up period. This is clinically relevant as it may enhance early cancer detection, potentially improving patient outcomes and survival rates.

Secondary objectives include:

• Comparing the proportion of patients receiving a cancer diagnosis at the initial allocated screening strategy.
• Assessing whether the extensive screening strategy, including FDG-PET/CT, enables the diagnosis of more early-stage cancers than the limited screening strategy.
• Determining if patients diagnosed with cancer are still alive after five years, indicating successful treatment of curable cancers.
• Evaluating the cost and effectiveness (cancers detected) of adding FDG-PET/CT to limited screening in patients with unprovoked VTE.
• Comparing the frequency of patients receiving additional tests following each strategy at screening and during follow-up.
• Developing a decision aid to assist patients in the decision-making process for cancer screening.

The clinical trial involves participants aged 50 years or older, both **male** and **female**, who have been newly diagnosed with a first unprovoked proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE) within the last four weeks. The study population is selected based on specific inclusion criteria, ensuring that participants have not experienced recent paralysis, paresis, or prolonged immobilization exceeding three days due to an acute medical condition, nor have they undergone major surgery requiring anesthesia in the past three months. Additionally, individuals with biological or clinical thrombophilia or active malignancy, except for adequately treated basal or squamous cell carcinoma, are excluded. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants' general health status is considered stable, with no active malignancy or health conditions suggesting the presence of cancer at the time of VTE diagnosis. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of adding **FDG-PET/CT** to a limited cancer screening strategy in patients aged 50 years or older with a first unprovoked venous thromboembolism (VTE). This is a randomized, controlled, and double-blind study, with a primary objective to determine if the addition of FDG-PET/CT reduces the number of missed cancer diagnoses compared to a limited screening strategy alone over a one-year follow-up period. The trial is expected to commence recruitment on September 10, 2024, and conclude by August 6, 2030.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, recent diagnosis of proximal deep vein thrombosis (DVT) or pulmonary embolism (PE), and absence of recent major surgery or active malignancy. Following the screening, eligible participants will be randomized into either the intervention group receiving FDG-PET/CT or the control group undergoing limited screening. Subsequent follow-up visits will be scheduled to monitor for new cancer diagnoses, assess early and advanced-stage tumors, and evaluate cancer-related mortality over a five-year period. The end-of-study visit will mark the completion of the one-year follow-up, during which the primary and secondary endpoints will be assessed.

The expected duration of participant involvement is one year, with conditions for early termination including the development of exclusion criteria such as new active malignancy or significant protocol deviations. The study will utilize **Gallium (68Ga) chloride** as a radiopharmaceutical agent, administered intravenously, with a maximum daily dose of 1850 MBq. The trial aims to provide valuable data to develop a decision aid for future cancer screening strategies, while also evaluating the cost-effectiveness of the screening methods employed.

The clinical trial involves the use of **Gallium (68Ga) Chloride** as the experimental medication. This compound is administered in the form of a **solution for injection**. The pharmaceutical product, known as GalliaPharm, is a radiopharmaceutical generator with an activity range of 0.74 to 1.85 GBq. The administration route for this medication is **intravenous**, ensuring direct delivery into the bloodstream. The maximum daily dose and total dose amount are both set at 1850 MBq, with a treatment period limited to one day. The active substance, Gallium (68Ga) Chloride, is of chemical origin and is classified under the ATC code V09X, which pertains to other diagnostic radiopharmaceuticals. The product is manufactured by Eckert & Ziegler Radiopharma GmbH and is not a pediatric formulation.

In this study, the experimental treatment is compared against a standard-of-care therapy, which includes a limited cancer screening strategy. The trial aims to evaluate the efficacy of adding FDG-PET/CT to this standard screening approach in detecting occult malignancies in patients with unprovoked venous thromboembolism. No placebo or additional comparator treatments are utilized in this trial. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol, although specific compliance measures are not detailed in the provided data.

Efficacy in this clinical trial will be assessed by evaluating the primary and secondary endpoints related to cancer detection in patients with unprovoked venous thromboembolism (VTE). The primary endpoint is the detection of **occult cancer** that is missed by the initial cancer screening strategy. This is defined as cancer diagnosed from the time of screening completion to the end of a 1-year follow-up period, which was not detected during the initial screening. Secondary endpoints include the diagnosis of new cancers after the initial screening, identification of early-stage and advanced-stage tumors, cancer-related mortality over a 5-year follow-up, and the economic evaluation of cancer diagnosis costs from the healthcare system's perspective over one year. The study will also assess additional tests required following each screening strategy and during follow-up, and the data will contribute to developing a decision aid for future cancer screening decisions.