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Surveillance AFter Extremity Tumor surgerY (SAFETY)

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ClinicalTrials.gov Identifier: NCT03944798
Recruitment Status : Recruiting
First Posted : May 10, 2019
Last Update Posted : March 11, 2021
Sponsor:
Collaborator:
Hamilton Academic Health Sciences Organization
Information provided by (Responsible Party):
McMaster University

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 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).

Condition or disease Intervention/treatment Phase
Soft Tissue Sarcoma Lung Metastases Other: Frequency: Every 3 Months Other: Frequency: Every 6 Months Other: Imaging Modality: Chest Radiograph (CXR) Other: Imaging Modality: Chest CT Not Applicable

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 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description: 2 x 2 factorial superiority randomized controlled trial
Masking: Single (Outcomes Assessor)
Masking Description:

The local clinical team, site study personnel and participants cannot be blinded to the treatment allocation as the imaging modalities are visually distinguishable and these individuals will be required to arrange the booking of surveillance visits and imaging at their respective clinical site.

The Central Adjudication Committee (CAC) will be blinded to surveillance frequency; however, because the imaging modalities are visually distinguishable, the CAC cannot be blinded to imaging modality. The data analysts will, however, remain blinded throughout the trial and all interpretation of study results will be conducted in a blinded manner. Since the primary outcome (overall survival) is objective, a lack of blinding of study personnel and patients, and the incomplete blinding of outcome assessors, introduces minimal threats to validity.

Primary Purpose: Prevention
Official Title: Surveillance AFter Extremity Tumor surgerY (SAFETY) International Randomized Controlled Trial
Actual Study Start Date : November 19, 2019
Estimated Primary Completion Date : November 2027
Estimated Study Completion Date : November 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Surveillance Arm I
Clinical assessment and chest radiograph (CXR) every six months for two years
Other: Frequency: Every 6 Months
every 6 months

Other: Imaging Modality: Chest Radiograph (CXR)
Chest radiograph (CXR)

Experimental: Surveillance Arm II
Clinical assessment and CXR every three months for two years
Other: Frequency: Every 3 Months
every 3 months

Other: Imaging Modality: Chest Radiograph (CXR)
Chest radiograph (CXR)

Experimental: Surveillance Arm III
Clinical assessment and chest computed tomography (CT) every six months for two years
Other: Frequency: Every 6 Months
every 6 months

Other: Imaging Modality: Chest CT
Chest computed tomography (CT)

Experimental: Surveillance Arm IV
Clinical assessment and chest CT every three months for two years
Other: Frequency: Every 3 Months
every 3 months

Other: Imaging Modality: Chest CT
Chest computed tomography (CT)




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: 5 years ]
    as measured by death from any cause.


Secondary Outcome Measures :
  1. Patient Anxiety [ Time Frame: 5 years ]
    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.

  2. Patient Satisfaction [ Time Frame: 5 years ]
    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.

  3. Patient Quality-of-Life [ Time Frame: 5 years ]
    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.

  4. Local Recurrence-Free Survival [ Time Frame: 5 years ]
    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. Metastasis-Free Survival [ Time Frame: 5 years ]
    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.

  6. Treatment-Related Complications [ Time Frame: 5 years ]
    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.

  7. Net Healthcare Costs [ Time Frame: 5 years ]
    Will include both the net costs of surveillance and costs incurred from metastasis treatment and metastasis treatment-related complications.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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);
  • The patient has been diagnosed with another malignancy within the past five years;
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03944798


Contacts
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Contact: Tricia Schneider 2892446087 schnep@mcmaster.ca
Contact: Victoria Giglio gigliovt@mcmaster.ca

Locations
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United States, California
University of California Davis Medical Center Recruiting
Sacramento, California, United States, 95817
Principal Investigator: Steven Thorpe, MD         
Sub-Investigator: R. Lor Randall, MD         
United States, Florida
University of Florida Health Shands Hospital Recruiting
Gainesville, Florida, United States, 32608
Principal Investigator: André Spiguel, MD         
United States, Iowa
Holden Comprehensive Cancer Center Recruiting
Iowa City, Iowa, United States, 52242
Principal Investigator: Benjamin Miller, MD, MS         
United States, New York
Albany Medical Center Recruiting
Albany, New York, United States, 12208
Principal Investigator: Matthew DiCaprio, MD         
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467
Principal Investigator: David Geller, MD         
NYU Langone Orthopaedic Hospital/Perlmutter Cancer Center Recruiting
New York, New York, United States, 10010
Principal Investigator: Karim Masrouha, MD         
Austria
LKH - Universitätsklinikum Graz Recruiting
Graz, Austria, 8036
Principal Investigator: Andreas Leithner, MD         
Sub-Investigator: Marko Bergovec, MD         
Canada, Ontario
Juravinski Hospital and Cancer Centre Recruiting
Hamilton, Ontario, Canada, L8V1C3
Contact: Tricia Schneider    289-244-6087    schnep@mcmaster.ca   
Contact: Victoria Giglio    905-550-2962    gigliovt@mcmaster.ca   
Principal Investigator: Michelle Ghert, MD, FRCSC         
Canada, Quebec
Hôpital Maisonneuve-Rosemont Recruiting
Montréal, Quebec, Canada, H1T 2M4
Principal Investigator: Georges Bastille, MD         
Sub-Investigator: Marc Isler, MD         
Sub-Investigator: Sophie Mottard, MD         
McGill University Health Centre Recruiting
Montréal, Quebec, Canada, H4A 3J1
Principal Investigator: Robert Turcotte, MD         
Hôtel Dieu du Quebec Recruiting
Québec, Quebec, Canada, G1R 2J6
Principal Investigator: Annie Arteau, MD         
Sub-Investigator: Norbert Dion, MD         
Sponsors and Collaborators
McMaster University
Hamilton Academic Health Sciences Organization
Investigators
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Principal Investigator: Michelle Ghert, MD, FRCSC McMaster University
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: McMaster University
ClinicalTrials.gov Identifier: NCT03944798    
Other Study ID Numbers: GHRT02
First Posted: May 10, 2019    Key Record Dates
Last Update Posted: March 11, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by McMaster University:
Soft Tissue Sarcoma
Lung Metastases
Overall Survival
Surveillance
Randomized Controlled Trial
Additional relevant MeSH terms:
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Neoplasm Metastasis
Sarcoma
Neoplastic Processes
Neoplasms
Pathologic Processes
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type