Clinical trial NCT04304651: Screening for Occult Malignancy in Patients with Unprovoked Venous Thromboembolism
Official title: Screening for Occult Malignancy Using 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) in Patients with Unprovoked Venous Thromboembolism
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Embolism and Thrombosis
Keywords: venous thrombosis
pulmonary embolism
screening
occult cancer
Lead sponsor: University Hospital, Brest
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
name: Canadian Institutes of Health Research (CIHR)
name: Ottawa Hospital Research Institute
First posted: 2020-03-11
Enrollment: 1276
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Occult cancer missed by screening strategies
timeFrame: At 1 year of follow-up
Secondary outcomes:
measure: Occult cancer diagnosed by screening strategies
timeFrame: At 1 month
measure: Early vs Adanced-stage cancers
timeFrame: At 1 year of follow-up
measure: Cancer-related mortality
timeFrame: At 5 years of follow-up
measure: Cost effectiveness analysis
timeFrame: At 1 year of follow-up
measure: Recurrent VTE
timeFrame: At 1 year of follow-up
measure: Decision aid to assist patients in the decision of cancer screening
timeFrame: At 1 year of follow-up
measure: Additional tests
timeFrame: At 1 year of follow-up
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Hopital Montfort
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montréal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Agen
country: France
facility: CH Agen
city: Angers
country: France
facility: CHU Angers
city: Brest
country: France
facility: Brest University Hospital
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
city: Dijon
country: France
facility: CHU de Dijon
city: Limoges
country: France
facility: CHU de Limoges
city: Morlaix
country: France
facility: CH des Pays de Morlaix
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Saint-Etienne
country: France
facility: CHU Saint-Etienne
city: Toulon
country: France
facility: Hôpital Saint Musse - CH Toulon
Study officials:
References:
citation: Robin P, Le Roux PY, Planquette B, Accassat S, Roy PM, Couturaud F, Ghazzar N, Prevot-Bitot N, Couturier O, Delluc A, Sanchez O, Tardy B, Le Gal G, Salaun PY; MVTEP study group. Limited screening with versus without (18)F-fluorodeoxyglucose PET/CT for occult malignancy in unprovoked venous thromboembolism: an open-label randomised controlled trial. Lancet Oncol. 2016 Feb;17(2):193-199. doi: 10.1016/S1470-2045(15)00480-5. Epub 2015 Dec 8.
citation: Carrier M, Lazo-Langner A, Shivakumar S, Tagalakis V, Zarychanski R, Solymoss S, Routhier N, Douketis J, Danovitch K, Lee AY, Le Gal G, Wells PS, Corsi DJ, Ramsay T, Coyle D, Chagnon I, Kassam Z, Tao H, Rodger MA; SOME Investigators. Screening for Occult Cancer in Unprovoked Venous Thromboembolism. N Engl J Med. 2015 Aug 20;373(8):697-704. doi: 10.1056/NEJMoa1506623. Epub 2015 Jun 22.
citation: van Es N, Le Gal G, Otten HM, Robin P, Piccioli A, Lecumberri R, Jara-Palomares L, Religa P, Rieu V, Rondina M, Beckers MM, Prandoni P, Salaun PY, Di Nisio M, Bossuyt PM, Buller HR, Carrier M. Screening for Occult Cancer in Patients With Unprovoked Venous Thromboembolism: A Systematic Review and Meta-analysis of Individual Patient Data. Ann Intern Med. 2017 Sep 19;167(6):410-417. doi: 10.7326/M17-0868. Epub 2017 Aug 22.