Surveillance AFter Extremity Tumor surgerY

Soft Tissue Sarcoma Clinical Trial

— SAFETY  

Official title:

Surveillance AFter Extremity Tumor surgerY (SAFETY) International Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03944798
• Other study ID #: GHRT02
• Status: Recruiting
• Phase: N/A
• Start date: November 19, 2019
• Est. completion date: December 2030

Study information

• Verified date: October 2022
• Source: McMaster University
• Contact: Tricia Schneider
• Phone: 2892446087
• Email: schnep[@]mcmaster.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 will randomize 830 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).

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 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). 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 soft-tissue sarcoma patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2030
• Est. primary completion date: December 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lung Metastases
• Neoplasm Metastasis
• Sarcoma
• Soft Tissue Sarcoma

Intervention

Other:
• Frequency: Every 3 Months
every 3 months
• Frequency: Every 6 Months
every 6 months
• Imaging Modality: Chest Radiograph (CXR)
Chest radiograph (CXR)
• Imaging Modality: Chest CT
Chest computed tomography (CT)

Locations

Country	Name	City	State
Argentina	Hospital Universitario Austral	Buenos Aires
Australia	St. Vincent's Hospital Melbourne	Fitzroy	Melbourne
Austria	LKH - Universitätsklinikum Graz	Graz
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre
Canada	Nova Scotia Health	Halifax	Nova Scotia
Canada	Juravinski Hospital and Cancer Centre	Hamilton	Ontario
Canada	Hôpital Maisonneuve-Rosemont	Montréal	Quebec
Canada	McGill University Health Centre	Montréal	Quebec
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Hôtel Dieu du Quebec	Québec	Quebec
Canada	Mount Sinai Hospital	Toronto	Ontario
Italy	Centro Traumatologico Ortopedico Hospital	Turin
Netherlands	Leiden University Medical Center	Leiden
United States	Albany Medical Center	Albany	New York
United States	Montefiore Medical Center	Bronx	New York
United States	Cleveland Clinic	Cleveland	Ohio
United States	Texas Tech Health Sciences Center	El Paso	Texas
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Parkview Cancer Institute	Fort Wayne	Indiana
United States	University of Florida Health Shands Hospital	Gainesville	Florida
United States	Hartford HealthCare	Hartford	Connecticut
United States	Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	NYU Langone Orthopaedic Hospital/Perlmutter Cancer Center	New York	New York
United States	Oregon Health and Science University Hospital	Portland	Oregon
United States	University of California Davis Medical Center	Sacramento	California
United States	Huntsman Cancer Institute	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
McMaster University	Hamilton Academic Health Sciences Organization

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Canada,  Italy,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	as measured by death from any cause.	5 years
Secondary	Patient Anxiety	The PROMIS® Cancer-Anxiety instrument assesses self-reported fear (fearfulness, panic), anxious misery (worry, dread), hyperarousal (tension, nervousness, restlessness), and somatic symptoms related to arousal (racing heart, dizziness). The PROMIS® Cancer-Anxiety instrument is a computer adaptive test. A minimum of 4 questions must be answered. One's responses will guide the system's choice of the next question. The test will continue until either the standard error drops below a specified level or the participant has answered the maximum number of 12 questions (whichever comes first). Each question has 5 response options ranging in value from 1 to 5. To find the raw score, sum the values of the response to each question. The lowest possible raw score is 4 and the highest is 60. The raw score will then be converted into a standardized T-score for each participant using the applicable conversion table. A higher T-score represents a higher degree of anxiety.	5 years
Secondary	Patient Satisfaction	The PROMIS® Satisfaction with Social Roles & Activities instrument assesses satisfaction with performing one's usual social roles and activities (e.g., 'I am satisfied with my ability to participate in family activities'). This instrument is a computer adaptive test. A minimum of 4 questions must be answered. One's response will guide the system's choice of the next question. The test will continue until either the standard error drops below a specified level or the participant has answered the maximum number of 12 questions (whichever comes first). Each question has 5 response options ranging in value from 1 to 5. To find the raw score, sum the values of the response to each question. The lowest possible raw score is 4 and the highest possible raw score is 60. The raw score will then be converted into a standardized T-score for each participant using the applicable conversion table. A higher T-score represents a higher degree of satisfaction.	5 years
Secondary	Patient Quality-of-Life	The validated EuroQol-5 Dimension 5-level (EQ-5D-5L) questionnaire measures generic health status and consists of 2 sections: the descriptive system and the Visual Analogue Scale (VAS). The descriptive system is comprised of 5 dimensions (mobility, self care, usual activities, pain / discomfort and anxiety / depression). Each question has 5 response options ranging in value from 1 to 5. To find the raw score, sum the values of the response to each question. The lowest possible raw score is 5 and the highest is 25. A lower raw score in the descriptive system represents fewer issues with each of the 5 domains. The VAS records a participant's self-rated health from 0 to 100 on a vertical VAS with endpoints labeled '100 - the best health you can imagine' and '0 - the worst health you can imagine'. The participant is asked to mark an 'X' on the scale and write the corresponding number, which is this section's raw score.	5 years
Secondary	Local Recurrence-Free Survival	As measured by the length of time from the time of randomization that the participant survives with no detection of recurrent disease at the initial tumor site or operative field.	5 years
Secondary	Metastasis-Free Survival	As measured by as the length of time from the time of randomization that the participant survives with no detection of systemic disease recurrence at any anatomic location.	5 years
Secondary	Treatment-Related Complications	Will include both chemotherapy-related complications, such as febrile neutropenia, fungal infections or sepsis, and thoracotomy-related complications, such as pneumothorax or surgical site infections.	5 years
Secondary	Net Healthcare Costs	Will include both the net costs of surveillance and costs incurred from metastasis treatment and metastasis treatment-related complications.	5 years

External Links

•   Optimal surveillance strategies following curative surgery for extremity sarcoma: A systematic review of Randomized Control Trials [published in pre-print].
•   Surveillance AFter Extremity Tumor surgerY (SAFETY): A Protocol for an International Randomized Controlled Trial [published in pre-print].