Screening for Occult Malignancy in Patients with Unprovoked Venous Thromboembolism

Not Applicable

Recruiting

• Conditions: Embolism and Thrombosis
• Interventions: Diagnostic Test: Limited cancer screening; Diagnostic Test: Limited cancer screening + FDG PET/CT

• Registration Number: NCT04304651
• Lead Sponsor: University Hospital, Brest

Brief Summary

Venous thromboembolism (VTE) can be the earliest sign of cancer. Identifying occult cancers at the time of VTE diagnosis may lead to significant improvement of patients' care. This is also an upmost issue for patients who want to know if an underlying cancer might have triggered the VTE.

An individual patient-level data meta-analysis (IPDMA) supports extensive screening strategies for occult cancer especially based on FDG PET/CT, and suggests that the best target population for cancer screening would be patients with unprovoked VTE older than 50 years of age (6.7% in patients aged 50 years or more vs. 1.0% in patients of less than 50 years (OR: 7.1, 95% CI: 3.1 to 16%).

Detailed Description

The identification of subgroups of patients at high risk of cancer might enable more efficient screening strategies for early detection of cancer. Venous thromboembolism (VTE) can be the first manifestation of an occult cancer. All tumor sites may be involved. In an individual patient-level data meta-analysis (IPDMA), it was reported a 1-year prevalence of occult cancer of 5.2% (95%CI 4.1-6.5) among patients presenting with unprovoked VTE.

Two recent multicenter randomized controlled trials (e.g. SOME (Canada) and MVTEP (France) trials) failed to demonstrate that extensive cancer screening strategies diagnosed more cancers, more early stage tumors, or improved cancer-related mortality in comparison with a more limited screening strategy. However, the main limitation of these studies was the twice lower than expected overall incidence of occult cancer diagnosis in unselected patients with unprovoked VTE, which limited the statistical power. In the IPDMA, it was also reported that the 1-year period prevalence of occult cancer was 7-fold higher in patients aged ≥ 50 (6.8%; 95%CI 5.6-8.3) as compared with those \< 50 years (1.0%; 95%CI 0.5-2.3).

Moreover, in the MVTEP trial, the incidence of missed cancers over a 2-years follow-up period was significantly lower in patients randomized to a 18F-Fluorodeoxyglucose Positron Emission/Computed Tomography (FDG-PET/CT) screening strategy. Thus, the most promising diagnostic modality for occult cancer screening seems to be FDG-PET/CT. FDG-PET/CT which allows a one-stop whole-body imaging, is routinely used for the diagnosis, staging and restaging of various cancers.

The MVTEP2 Trial seeks to determine if among higher risk patients (≥ 50 year-old) with a first unprovoked VTE, a cancer screening strategy including a FDG-PET/CT decreases the number of missed occult cancers detected over a 1-year follow-up period as compared with a limited screening alone.

Study Timeline

• Study First Submitted: 2020-03-07
• Study First Submitted QC: 2020-03-10
• Study First Posted: 2020-03-11
• Study Start: 2020-09-08
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-13
• Last Update Posted: 2024-12-16
• Primary Completion: 2026-09-08
• Study Completion: 2030-09-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1276

Inclusion Criteria

Patients aged 50 years or older with a new diagnosis of first unprovoked proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE) will be eligible to participate into the study.

Unprovoked VTE is defined as the absence of any of the following predisposing factors:

1. active malignancy (known malignancy, progressive and/or treated during the last 5 years) except for adequately treated basal or squamous cell carcinoma; Patients whose state of health suggests the presence of cancer at the time of diagnosis of VTE cannot be included in the protocol
2. recent (less than 3 months) paralysis, paresis or plaster immobilization of the lower extremities;
3. recently bedridden for period of 3 or more days, or major surgery, within the previous 12 weeks requiring general or regional anaesthesia;
4. previous unprovoked VTE;
5. known thrombophilia (hereditary or acquired)

Exclusion Criteria

Patients will be excluded from the study if they have any of the following criteria:

1. Refusal or inability to provide informed consent;
2. Hypersensitivity to 18F-FDG or any of the excipients according to the product monograph;
3. Unavailable to follow-up.
4. VTE while on anticoagulation (e.g apixaban, rivaroxaban, edoxaban, dabigatran, warfarin)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Limited cancer screening	Limited cancer screening	Limited screening alone.
Limited cancer screening + FDG PET/CT	Limited cancer screening + FDG PET/CT	Limited screening + FDG PET/CT

Primary Outcome Measures

Name	Time	Method
Occult cancer missed by screening strategies	At 1 year of follow-up	Occult cancer "missed" by cancer screening defined as proven cancer diagnosed (either biopsy proven cancer or cancer diagnosis approved by adjudication committee in the absence of biopsy proven cancer) from the time of cancer screening completion to the end of the 1-year follow-up period, and not detected at the time of screening. In other words, "missed" means the number of new cancers diagnosed in patients considered not to have cancer after having completed the assigned cancer screening strategy (i.e false negative results of screening strategies).

Secondary Outcome Measures

Name	Time	Method
Cancer-related mortality	At 5 years of follow-up	Cancer-related mortality during a 5-year follow-up period.
Occult cancer diagnosed by screening strategies	At 1 month	The proportion of patients with a new cancer diagnosis after completion of the initial allocated screening strategy.
Recurrent VTE	At 1 year of follow-up	Rate of recurrent VTE
Decision aid to assist patients in the decision of cancer screening	At 1 year of follow-up	Development of a decision aid to assist patients in the decision of cancer screening
Early vs Adanced-stage cancers	At 1 year of follow-up	The proportion of early-stage (T1-2N0M0) as per the World Health Organization TNM classification system) versus advanced-stage tumors at initial screening and during follow-up.
Additional tests	At 1 year of follow-up	The proportion of patients receiving additional tests following each strategy
Cost effectiveness analysis	At 1 year of follow-up	Additional cost per additional cancer detected.

Trial Locations

Locations (20)

University of Calgary; 🇨🇦 Calgary, Alberta, Canada

University of Manitoba; 🇨🇦 Winnipeg, Manitoba, Canada

McMaster University; 🇨🇦 Hamilton, Ontario, Canada

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

Hopital Montfort; 🇨🇦 Ottawa, Ontario, Canada

Ottawa Hospital Research Institute; 🇨🇦 Ottawa, Ontario, Canada

Sunnybrook Research Institute; 🇨🇦 Toronto, Ontario, Canada

University Health Network; 🇨🇦 Toronto, Ontario, Canada

Jewish General Hospital; 🇨🇦 Montréal, Quebec, Canada

McGill University Health Centre; 🇨🇦 Montréal, Quebec, Canada

CH Agen; 🇫🇷 Agen, France

CHU Angers; 🇫🇷 Angers, France

Brest University Hospital; 🇫🇷 Brest, France

CHU de Clermont-Ferrand; 🇫🇷 Clermont-Ferrand, France

CHU de Dijon; 🇫🇷 Dijon, France

CHU de Limoges; 🇫🇷 Limoges, France

CH des Pays de Morlaix; 🇫🇷 Morlaix, France

Hôpital Européen Georges Pompidou; 🇫🇷 Paris, France

CHU Saint-Etienne; 🇫🇷 Saint-Etienne, France

Hôpital Saint Musse - CH Toulon; 🇫🇷 Toulon, France