High Grade Sarcoma, Sarcoma
Conditions
Brief summary
This phase II trial compares standard of care surgical resection to fluorescence-guided surgical resection using indocyanine green and fluorescence imaging for reducing unexpected positive margin rates in patients with sarcoma. Surgical margins are one of the criteria used in assessing the effectiveness of a given surgical procedure. They are the edges or border of the tissue removed in cancer surgery. A negative margin means that the resected tumor is surrounded by normal tissue, which implies there is no disease left in the patient. By contrast, a positive margin means that sarcoma cells are visible at the edge of the tumor. Positive margins may be classified as planned when they are expected pre-operatively due to the preservation of a critical structure, or unexpected when the pathologist reports the presence of tumor at the margin despite the surgeon having intended to remove it in its entirety. Fluorescence-guided surgery is an established surgical method that involves the administration of fluorescent dye (in this case, indocyanine green) into the tumor, which can then be visualized with a special camera during surgery to help surgeons identify tumor versus healthy tissue. Fluorescence-guided surgery may reduce the rate of unexpected positive margins in patients undergoing surgery for sarcoma.
Detailed description
PRIMARY OBJECTIVE: I. To determine whether there is a reduction in the unexpected positive margin rate (UPM) in patients receiving fluorescence-guided surgery (FGS) using indocyanine green (ICG) compared to standard of care (SoC). SECONDARY OBJECTIVE: I. To determine the effect of FGS using ICG compared to the SoC over a 12-month period. EXPLORATORY OBJECTIVE: I. To determine the role of ICG in the pathological margin assessment of resected sarcoma specimens whilst improving understanding of the cellular mechanisms of FGS using ICG. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo standard of care surgical resection. ARM II: Patients receive ICG intravenously (IV) 12-24 hours prior to their scheduled surgery. Patients then undergo FGS with intraoperative fluorescence imaging. After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months.
Interventions
OTHERElectronic Health Record Review
Ancillary studies
PROCEDUREFluorescence Imaging
Undergo fluorescence imaging
PROCEDUREFluorescence-Guided Surgery
Undergo FGS
DRUGIndocyanine Green
Given IV
OTHERQuestionnaire Administration
Ancillary studies
PROCEDUREResection
Undergo surgical resection
Sponsors
City of Hope Medical Center
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The histopathology staff and senior trial statistician will be blinded and unaware of the surgery type to allow for blinded measurement and analysis of primary outcome.
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Documented written informed consent of the participant * Histologically confirmed diagnosis of intermediate to high grade sarcoma * All ages * Amenable to surgical resection as a part of curative intent for the patient * Willingness to: * Respond to surveys during the trial * Permit medical record/ clinical laboratory result review
Exclusion criteria
* Due for surgery with palliative intent * Recurrent tumors * Intracranial, retroperitoneal, and visceral anatomical locations * A woman of childbearing potential who is currently pregnant (as confirmed by urine pregnancy test) * A woman who are currently breastfeeding * Known allergies to ICG, iodine, iodine dyes or shellfish * Unable to provide written and informed consent * Patients with hyper-thyroidism or autonomic thyroid adenomas * Premature infants/neonates with exchange transfusion indication due to hyperbilirubinemia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Unexpected positive margin (UPM) rate | At 6 months post-surgery | The margin status of each tumor will be taken from the pathology report for each patient enrolled in the trial. This will be recorded at six months post- surgery and will be classified according to the R classification system. The UPM rate for each arm will be defined by calculating the percentage of patients in that arm with a UPM on histopathological assessment of the resection specimen. The percentage of patients with unexpected positive margins will be calculated for each group to give the unexpected positive margin rate. This will then be compared between the two groups. Will use a logistic regression that adjusts key covariates including stratification factors used in the randomization. A Wald test and a 95% confidence interval will be extracted from this model. A two-sided p-value will be found from the Wald test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intraoperative complications | During surgical resection | Intraoperative complications may include blood loss requiring transfusion, inadvertent damage to nerves, inadvertent damage to tendons/ligaments, inadvertent damage to bony structures, myocardial infarction, stroke, other events determined by the principal investigator to be a complication of the surgery. Will be compared between the two groups at the day of operation. Descriptive analysis will be performed to analyze the nature of the data. Secondary outcomes with binary/multiple measures will be analyzed with logistic regression. For variables with continuous measure, appropriate regression models will be used. Appropriate statistical tests depending on the nature of the variables (whether qualitative or quantitative) will be used for comparison between the two treatment arms. |
| Postoperative complications | Up to 12 months | Postoperative complications may include wound infection, wound dehiscence, seroma, flap complications, deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, other events determined by the principal investigator to be a complication of the surgery. Post operative complications will be graded using the Calvien Dindo Classifications of Surgical Complications. Will be compared between the two groups at the day of operation and at 1-, 6- and 12-month follow-up time points. Descriptive analysis will be performed to analyze the nature of the data. Secondary outcomes with binary/multiple measures will be analyzed with logistic regression. For variables with continuous measure, appropriate regression models will be used. Appropriate statistical tests depending on the nature of the variables (whether qualitative or quantitative) will be used for comparison between the two treatment arms. |
| Length of index operation | During surgical resection | Will be measured in minutes. Will be compared between groups on the day of operation. Descriptive analysis will be performed to analyze the nature of the data. Secondary outcomes with binary/multiple measures will be analyzed with logistic regression. For variables with continuous measure, appropriate regression models will be used. Appropriate statistical tests depending on the nature of the variables (whether qualitative or quantitative) will be used for comparison between the two treatment arms. |
| Length of inpatient stay | Through study completion, an average of 1 year | Will be measured in days. Will be compared between the two groups at the day of operation and at 1-, 6- and 12-month follow-up time points. Descriptive analysis will be performed to analyze the nature of the data. Secondary outcomes with binary/multiple measures will be analyzed with logistic regression. For variables with continuous measure, appropriate regression models will be used. Appropriate statistical tests depending on the nature of the variables (whether qualitative or quantitative) will be used for comparison between the two treatment arms. |
| Recurrence | Up to 12 months | Local/regional/distal recurrence is defined as the recurrence of sarcoma at the site of primary resection (local) or at a site other than that of the primary tumor, including distal metastasis. Investigations must be tailored to circumstances but where possible should include histological confirmation. Will be compared between the two groups at the 12-month time point. Descriptive analysis will be performed to analyze the nature of the data. Secondary outcomes with binary/multiple measures will be analyzed with logistic regression. For variables with continuous measure, appropriate regression models will be used. Appropriate statistical tests depending on the nature of the variables (whether qualitative or quantitative) will be used for comparison between the two treatment arms. |
| Therapies | Up to 12 months | Adjuvant and neo-adjuvant therapy rates will include radiation therapy and/or chemotherapy. The type and frequency of therapy will be recorded. Will be compared between groups on the day of operation. Descriptive analysis will be performed to analyze the nature of the data. Secondary outcomes with binary/multiple measures will be analyzed with logistic regression. For variables with continuous measure, appropriate regression models will be used. Appropriate statistical tests depending on the nature of the variables (whether qualitative or quantitative) will be used for comparison between the two treatment arms. |
| Overall survival | Up to 12 months | Overall survival is defined as death due to any cause. Where possible, the specific cause of death should be documented, allowing the calculation of disease specific survival. Will be compared between the two groups at the 12-month time point. Descriptive analysis will be performed to analyze the nature of the data. Survival analysis like the Kaplan-Meier statistics will be used to find the overall survival in each arm. Appropriate statistical tests depending on the nature of the variables (whether qualitative or quantitative) will be used for comparison between the two treatment arms. |
| Quality of life | Up to 12 months | Quality of life will be assessed using the EQ-5D-5L European Quality of Life Five Dimension Five Level scale or European Quality of Life Five Dimension Three Level Youth scale. Will be compared between the two groups. Descriptive analysis will be performed to analyze the nature of the data. Secondary outcomes with binary/multiple measures will be analyzed with logistic regression. For variables with continuous measure, appropriate regression models will be used. Appropriate statistical tests depending on the nature of the variables (whether qualitative or quantitative) will be used for comparison between the two treatment arms. |
| Recovery following resection | Up to 12 months | After undergoing surgical resection for sarcomas of the extremity, participants are often left with an element of functional impairment in the affected limb due to the extent of the resection required. There are separate questionnaires for participants undergoing surgery on the upper and lower extremities, in which participants are asked to rate their ability to perform several tasks, rating them from 'impossible' to 'not at all difficult', as well as overall rating of how disabled they feel they are. Descriptive analysis will be performed to analyze the nature of the data. Secondary outcomes with binary/multiple measures will be analyzed with logistic regression. For variables with continuous measure, appropriate regression models will be used. Appropriate statistical tests depending on the nature of the variables (whether qualitative or quantitative) will be used for comparison between the two treatment arms. |
| Surgical impact and decision making | Immediately following surgical resection | Immediately following the surgical procedure, a surgical case report form (CRF) will be completed by the surgeon who performed the surgery. This CRF will record if there was the potential for an acceptable close/positive margin due to the preservation of a critical structure, the length of the operation and any intra-operative complications. If the participant was randomized to the intervention arm, the CRF will also record whether the surgeon felt this influenced their operative decision making. Descriptive analysis will be performed to analyze the nature of the data. Secondary outcomes with binary/multiple measures will be analyzed with logistic regression. For variables with continuous measure, appropriate regression models will be used. Appropriate statistical tests depending on the nature of the variables (whether qualitative or quantitative) will be used for comparison between the two treatment arms. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORThinzar Lwin
City of Hope Medical Center
Outcome results
None listed