Clinical trial NCT03944798: Surveillance AFter Extremity Tumor surgerY
Official title: Surveillance AFter Extremity Tumor surgerY (SAFETY) International Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Soft Tissue Sarcoma
Lung Metastases
Keywords: Soft Tissue Sarcoma
Lung Metastases
Overall Survival
Surveillance
Randomized Controlled Trial
Patient Anxiety
Serious Adverse Events
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Hamilton Academic Health Sciences Organization
name: Canadian Cancer Society (CCS)
name: Canadian Institutes of Health Research (CIHR)
name: American Academy of Orthopaedic Surgeons
name: Musculoskeletal Tumor Society
First posted: 2019-05-10
Enrollment: 310
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: 2 x 2 factorial superiority randomized controlled trial
Primary purpose: PREVENTION

Brief summary: Following treatment for a primary extremity sarcoma, patients remain at risk for the development of local and systemic disease recurrence. Metastasis (distant recurrence) to the lung is the most frequent single location of disease recurrence in sarcoma patients, occurring in almost half of all patients. Therefore, careful post-operative surveillance is an integral element of patient care. However, the detection of metastases does not necessarily affect long-term survival and may negatively impact quality of life. Surveillance strategies have not been well researched and have been identified as the top research priority in the extremity sarcoma field. Using a 2X2 factorial design to maximize efficiency and reduce overall trial costs, the SAFETY trial randomized 310 extremity soft-tissue sarcoma (STS) patients to determine the effect of surveillance strategy on overall patient survival after surgery for a STS of the extremity by comparing the effectiveness of both surveillance frequency (every 3 vs. every 6 months) and imaging modality (CT scans vs. chest radiographs).

Detailed description: Post-treatment STS surveillance is an integral element of patient care. Although earlier detection of metastatic disease may improve long-term survival, no study has yet provided definitive evidence to support this assumption. A thorough systematic review of the literature has identified only a single limited randomized controlled trial (RCT) evaluating this clinical question, and surveys of sarcoma surgeons have determined that surgeons typically follow their patients based on the way in which they were trained. The orthopaedic oncology field has identified sarcoma surveillance strategy as the top research priority in the field. In order to fill the evidence gap in sarcoma surveillance, a large international RCT is required. The investigators, therefore, propose the Surveillance AFter Extremity Tumor surgerY (SAFETY) trial. In preparation for the SAFETY trial, the SAFETY investigators have completed the following preparatory work: A) establishment of a worldwide research collaborative group that spans 6 continents; B) collection of data from international sarcoma patients to determine their perceptions of sarcoma surveillance and their willingness to participate in a study in which randomization will determine their follow-up protocols; and C) the organization of a large Protocol Development Meeting with international and multidisciplinary participation, including sarcoma patient involvement, where critical aspects of the protocol were discussed and finalized.

The international, multi-center SAFETY trial will determine the effect of surveillance strategy on patient-important outcomes after surgery for a STS of the extremity by comparing the effectiveness of both surveillance frequency (every 3 vs. every 6 months) and imaging modality (CT scans vs. chest radiographs). Ultimately, the SAFETY trial will provide the necessary evidence to develop evidence-based surveillance guidelines, and is poised to have a significant impact on the post-operative care and outcomes of extremity STS patients.

Eligibility criteria: Inclusion Criteria:

* The patient is 18 years of age or older;
* The patient has been diagnosed with a primary extremity grade II or III soft-tissue sarcoma (STS);
* The patient has undergone surgical excision of the tumor with curative intent and with no evidence of gross residual disease based on the pathology report;
* The patient has completed all planned neoadjuvant or adjuvant radiation and / or chemotherapy, if applicable;
* The tumor size is greater than or equal to (≥) five centimeters according to the pathology report or based on the pre-treatment MRI if neoadjuvant radiation and / or chemotherapy are given; and
* The patient provides informed consent.

Exclusion Criteria:

* The patient has metastases at initial presentation based on the radiology report of the initial thoracic imaging†;
* The patient has recently undergone surgical excision of a local recurrence;
* The patient has been diagnosed with one of the special sub-types, myxoid / round cell liposarcoma or extra-skeletal Ewing's sarcoma\*;
* The patient has been previously diagnosed with a genetic syndrome with an elevated risk of malignancy, such as Li-Freumeni Syndrome‡;
* The patient has been previously diagnosed with a co-morbid condition that has a life expectancy of less than (\<) one year;
* The site-specific surveillance protocol for the patient's disease is not compatible with the study protocol (i.e., regular planned whole-body imaging with positron emission tomography \[PET\] scans);
* Likely problems, in the judgment of the investigator, with the patient maintaining follow-up (with the specific reasoning requiring approval of the Methods Center);
* The patient is currently enrolled in a study that does not permit co-enrolment; and
* The patient has already been enrolled in the SAFETY trial.

  * A second CT scan may be required to confirm that indeterminate nodules are false positives before the patient can be enrolled (provided that the second CT scan shows no evidence of metastatic disease);

    * Myxoid liposarcoma and extra-skeletal Ewing's sarcoma have different metastatic patterns, which necessitate different surveillance protocols;

      * Individuals with Li-Freumeni Syndrome, or other genetic syndromes with an elevated risk of malignancy, appear to be at an elevated risk for radiation-induced cancers, so the use of CT scans should be limited.

Primary outcomes:
measure: Hierarchal Composite Outcome of Patient-Important Outcomes
timeFrame: 3 years post randomization
Secondary outcomes:
measure: Patient Anxiety
timeFrame: 3 years
measure: Patient Satisfaction
timeFrame: 3 years
measure: Patient Quality-of-Life
timeFrame: 3 years
measure: Local Recurrence-Free Survival
timeFrame: 3 years
measure: Metastasis-Free Survival
timeFrame: 3 years
measure: Treatment-Related Complications
timeFrame: 3 years
measure: Net Healthcare Costs
timeFrame: 3 years
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Hartford
country: United States
facility: Hartford HealthCare
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida Health Shands Hospital
state: Florida
city: Chicago
country: United States
facility: UChicago Medicine
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Cancer Institute
state: Indiana
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center
state: Iowa
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: NYU Langone Orthopaedic Hospital/Perlmutter Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University Hospital
state: Oregon
city: Monroeville
country: United States
facility: Allegheny Health Network Research Institute
state: Pennsylvania
city: El Paso
country: United States
facility: Texas Tech Health Sciences Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Buenos Aires
country: Argentina
facility: Hospital Universitario Austral
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital Melbourne
state: Melbourne
city: Graz
country: Austria
facility: LKH - Universitätsklinikum Graz
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
city: Halifax
country: Canada
facility: Nova Scotia Health
state: Nova Scotia
city: Hamilton
country: Canada
facility: Juravinski Hospital and Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Montréal
country: Canada
facility: Hôpital Maisonneuve-Rosemont
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Québec
country: Canada
facility: Hôtel Dieu du Quebec
state: Quebec
city: Berlin
country: Germany
facility: Helios Klinikum Berlin
city: Turin
country: Italy
facility: Centro Traumatologico Ortopedico Hospital
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Kuala Lumpur
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitario de Coimbra
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
affiliation: McMaster University
name: Michelle Ghert, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: SAFETY Investigators. The Surveillance After Extremity Tumor Surgery (SAFETY) trial: protocol for a pilot study to determine the feasibility of a multi-centre randomised controlled trial. BMJ Open. 2019 Sep 18;9(9):e029054. doi: 10.1136/bmjopen-2019-029054.