Screening for Occult Malignancy in Patients With Unprovoked Venous Thromboembolism

Embolism and Thrombosis Clinical Trial

— MVTEP2/SOME2  

Official title:

Screening for Occult Malignancy Using 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) in Patients With Unprovoked Venous Thromboembolism

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04304651
• Other study ID #: 29BRC20.0021
• Status: Recruiting
• Phase: N/A
• Start date: September 8, 2020
• Est. completion date: September 8, 2030

Study information

• Verified date: March 2024
• Source: University Hospital, Brest
• Contact: Pierre-Yves SALAUN
• Phone: (+33)298223327
• Email: pierre-yves.salaun[@]chu-brest.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1276
• Est. completion date: September 8, 2030
• Est. primary completion date: September 8, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Embolism
• Embolism and Thrombosis
• Thromboembolism
• Thrombosis
• Venous Thromboembolism

Intervention

Diagnostic Test:
• Limited cancer screening
The limited cancer screening will include: 1) a complete medical history and physical examination; 2) complete blood count; 3) liver function tests (AST, ALT, ALP, bilirubin); and 4) chest X-ray. In women, a breast examination, Pap smear/pelvic examination (if < 70 years old and previously sexually active) and mammogram will be performed, if not conducted in last year. In men, similarly, prostate examination and PSA testing will be performed, if not conducted in the last year. All patients will undergo colon cancer screening as per local practice.
• Limited cancer screening + FDG PET/CT
The limited cancer screening (as described above) in combination with a FDG PET/CT.

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	McMaster University	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Jewish General Hospital	Montréal	Quebec
Canada	McGill University Health Centre	Montréal	Quebec
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	University of Manitoba	Winnipeg	Manitoba
France	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

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital, Brest	Canadian Institutes of Health Research (CIHR), Ministry of Health, France, Ottawa Hospital Research Institute

Countries where clinical trial is conducted

Canada,  France, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occult cancer missed by screening strategies	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).	At 1 year of follow-up
Secondary	Occult cancer diagnosed by screening strategies	The proportion of patients with a new cancer diagnosis after completion of the initial allocated screening strategy.	At 1 month
Secondary	Early vs Adanced-stage cancers	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.	At 1 year of follow-up
Secondary	Cancer-related mortality	Cancer-related mortality during a 5-year follow-up period.	At 5 years of follow-up
Secondary	Cost effectiveness analysis	Additional cost per additional cancer detected.	At 1 year of follow-up
Secondary	Recurrent VTE	Rate of recurrent VTE	At 1 year of follow-up
Secondary	Decision aid to assist patients in the decision of cancer screening	Development of a decision aid to assist patients in the decision of cancer screening	At 1 year of follow-up
Secondary	Additional tests	The proportion of patients receiving additional tests following each strategy	At 1 year of follow-up