Screening for Occult Malignancy in Patients With Unprovoked Venous Thromboembolism (MVTEP2/SOME2)

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

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%).

Study Overview

• Status: Recruiting
• Conditions: Embolism and Thrombosis
• Intervention / Treatment: Diagnostic test: Limited cancer screening; Diagnostic test: Limited cancer screening + FDG PET/CT

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 Type: Interventional
• Enrollment (Estimated): 1276
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pierre-Yves SALAUN; Phone Number: (+33)298223327; Email: pierre-yves.salaun@chu-brest.fr
• Study Contact Backup: Name: Aurélien DELLUC; Email: adelluc@toh.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Not yet recruiting
      • University of Calgary
      • Contact: Leslie Skeith
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • Not yet recruiting
      • University of Manitoba
      • Contact: Ryan Zarychanski
  • Ontario
    • Hamilton, Ontario, Canada
      • Not yet recruiting
      • McMaster University
      • Contact: Deborah Siegal
    • London, Ontario, Canada
      • Not yet recruiting
      • London Health Sciences Centre
      • Contact: Alejandro Lazno-Langner
    • Ottawa, Ontario, Canada
      • Recruiting
      • Ottawa Hospital Research Institute
      • Contact: Aurélien DELLUC; Email: adelluc@toh.ca
      • Contact: Marc CARRIER; Email: mcarrier@toh.ca
      • Sub-Investigator: Grégoire LE GAL
    • Ottawa, Ontario, Canada
      • Recruiting
      • Hopital Montfort
      • Contact: Gregoire Le Gal
    • Toronto, Ontario, Canada
      • Recruiting
      • Sunnybrook Research Institute
      • Contact: Jean-Phillippe Galanaud
    • Toronto, Ontario, Canada
      • Recruiting
      • University Health Network
      • Contact: Erik Yeo
      • Contact: Jameel Abdulrehman
  • Quebec
    • Montréal, Quebec, Canada
      • Recruiting
      • Jewish General Hospital
      • Contact: Vicky Tagalakis
    • Montréal, Quebec, Canada
      • Not yet recruiting
      • McGill University Health Centre
      • Contact: Susan Solymoss
• France
  • Agen, France
    • Recruiting
    • CH Agen
    • Contact: RORIZ Mélanie; Email: rorizm@ch-agen-nerac.fr
    • Sub-Investigator: Alexandre-Xavier BOISSON
  • Angers, France
    • Recruiting
    • Chu Angers
    • Contact: Pierre-Marie ROY
  • Brest, France
    • Recruiting
    • Brest University Hospital
    • Contact: Pierre-Yves SALAUN; Email: pierre-yves.salaun@chu-brest.fr
    • Contact: Philippe ROBIN; Email: philippe.robin@chu-brest.fr
    • Sub-Investigator: Francis COUTURAUD
    • Sub-Investigator: Pierre-Yves LE ROUX
  • Clermont-Ferrand, France
    • Recruiting
    • CHU de Clermont-Ferrand
    • Contact: Jeannot SCHMIDT
  • Dijon, France
    • Recruiting
    • CHU de Dijon
    • Contact: Nicolas FALVO
  • Limoges, France
    • Recruiting
    • CHU de Limoges
    • Contact: Philippe LACROIX
  • Morlaix, France, 29600
    • Recruiting
    • CH des Pays de Morlaix
    • Contact: David RENAUD, Dr; Email: Drenault@ch-morlaix.fr
  • Paris, France
    • Recruiting
    • Hopital Europeen Georges Pompidou
    • Contact: Olivier SANCHEZ
  • Saint-Etienne, France
    • Recruiting
    • CHU Saint-Etienne
    • Contact: Laurent BERTOLETTI
  • Toulon, France
    • Recruiting
    • Hôpital Saint Musse - CH Toulon
    • Contact: Antoine ELIAS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Limited cancer screening; Limited screening alone.	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.
Experimental: Limited cancer screening + FDG PET/CT; Limited screening + FDG PET/CT	Diagnostic test: Limited cancer screening + FDG PET/CT; The limited cancer screening (as described above) in combination with a FDG PET/CT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Cancer-related mortality	Cancer-related mortality during a 5-year follow-up period.	At 5 years of follow-up
Cost effectiveness analysis	Additional cost per additional cancer detected.	At 1 year of follow-up
Recurrent VTE	Rate of recurrent VTE	At 1 year of follow-up
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
Additional tests	The proportion of patients receiving additional tests following each strategy	At 1 year of follow-up

Collaborators and Investigators

• Sponsor: University Hospital, Brest
• Collaborators: Canadian Institutes of Health Research (CIHR); Ministry of Health, France; Ottawa Hospital Research Institute

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2020
• Primary Completion (Estimated): September 8, 2026
• Study Completion (Estimated): September 8, 2030

Study Registration Dates

• First Submitted: March 7, 2020
• First Submitted That Met QC Criteria: March 10, 2020
• First Posted (Actual): March 11, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: screening; venous thrombosis; pulmonary embolism; occult cancer
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism; Thrombosis; Thromboembolism; Venous Thromboembolism; Embolism and Thrombosis
• Other Study ID Numbers: 29BRC20.0021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected data that underlie results in a publication
• IPD Sharing Time Frame: Data will be available beginning three years and ending fifteen years following the final study report completion
• IPD Sharing Access Criteria: Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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