ICG Guided Surgery for Cancer

Overseen By Abdelhafeez Abdelhafeez, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: Iodide allergies, Brain tumors, Pregnant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

230 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a study to assess the ability of Indocyanine Green (ICG) to identify neoplastic disease. For many pediatric solid tumors, complete resection of the primary site and/or metastatic deposits is critical for achieving a cure. An optimal intra-operative tool to help visualize tumor and its margins would be of benefit. ICG real-time fluorescence imaging is a technique being used increasingly in adults for this purpose. We propose to use it during surgery for pediatric malignancies. All patients with tumors that require localization for resection or biopsy of the tumor and/or metastatic lesions will be eligible. Primary Objective To assess the feasibility of Indocyanine Green (ICG)-mediated near-infrared (NIR) imagery to identify neoplastic disease during the conduct of surgery to resect neoplastic lesions in children and adolescents. NIR imaging will be done at the start of surgery to assess NIR-positivity of the lesion(s) and at the end of surgery to assess completeness of resection. Separate assessments will be made for the following different histologic categories: 1. Osteosarcoma 2. Neuroblastoma 3. Metastatic pulmonary deposits - closed to accrual Exploratory Objectives 1. To compare the ICG uptake by primary vs metastatic site and pre-treated (chemotherapy, radiation, or both) vs non-pre-treated. 2. Assess the sensitivity and specificity of NIR imagery to find additional lesions not identified by standard of care intraoperative inspection and tactile feedback. 3. Assess the sensitivity and specificity of NIR imagery to find additional lesions not identified on preoperative diagnostic imaging. 4. Assess the sensitivity and specificity of NIR imagery for identifying residual disease at the conclusion of a tumor resection. Separate assessments will be made for the following different histologic categories based on their actual enrollment; this includes but is not limited to analyzing multiple arms together: 1. Ewing Sarcoma 2. Rhabdomyosarcoma (RMS) 3. Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS) 4. Renal tumors 5. Liver tumors, lymphoma, other rare tumors, and nodules of unknown etiology

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Indocyanine Green (ICG) Guided Surgery for Cancer?

Research shows that Indocyanine Green (ICG) is effective in enhancing surgical outcomes by improving visualization of anatomical structures, which helps in identifying and removing tumors more safely and accurately. It has been successfully used in various surgeries, including colorectal and breast cancer, to detect lymph nodes and improve tumor localization. ^{1 2 3 4 5}

Is indocyanine green (ICG) safe for use in humans?

Indocyanine green (ICG) is generally used safely in various surgeries, but there have been reports of severe reactions, such as hemodynamic instability (serious blood flow issues) during heart surgery. While it is commonly used in procedures like breast cancer and gastric cancer surgeries, some studies note a lack of comprehensive safety data, and there are proposed guidelines for managing adverse reactions. ^{6 7 8 9 10}

How is the treatment Indocyanine Green (ICG) guided surgery unique for cancer?

Indocyanine Green (ICG) guided surgery is unique because it uses a special dye that lights up under near-infrared light, helping surgeons see and remove cancerous tissues more precisely during surgery. This approach enhances visualization of tumors and lymph nodes in real-time, which is different from traditional methods that rely on visual inspection and palpation. ^{3 11 12 13 14}

Research Team

Lindsay Talbot, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

This trial is for children and adolescents who need surgery to remove or biopsy solid tumors or lymphoma, including metastatic lesions. It's not for those with unilateral Wilms Tumor, benign pathology, brain tumors, or iodide allergies.

Inclusion Criteria

I need surgery for my solid tumor or lymphoma, whether it's the first occurrence or a relapse.

Exclusion Criteria

You are allergic to iodine.

I have Wilms Tumor in one kidney.

I am willing and able to give written consent for the trial.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Surgery Preparation

Participants receive a single dose of Indocyanine Green (ICG) intravenously prior to surgery

1 day

1 visit (in-person)

Surgery

Surgical resection of tumors using ICG-mediated near-infrared (NIR) imagery to identify neoplastic disease

1 day

1 visit (in-person)

Immediate Post-Surgery Monitoring

Participants are monitored for 24 hours post-surgery for safety and effectiveness of the procedure

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Indocyanine Green

Trial Overview The study tests Indocyanine Green (ICG) guided imaging during surgery to see if it helps identify cancerous tissue in real-time. It aims to improve the precision of tumor removal in various cancers like osteosarcoma and neuroblastoma.

Participant Groups

Group I: Indocyanine green (ICG) Experimental Treatment 1 Intervention

Participants will receive a single dose of 1.5 mg/kg of ICG intravenously over 15 minutes prior to surgery.

Indocyanine Green is already approved in United States, European Union, China, Japan for the following indications:

Approved in United States as Indocyanine Green for:

• Diagnostic imaging agent for various medical procedures including sentinel lymph node mapping

Approved in European Union as Indocyanine Green for:

• Diagnostic imaging agent for various medical procedures including sentinel lymph node mapping

Approved in China as Indocyanine Green for:

• Diagnostic imaging agent for various medical procedures including sentinel lymph node mapping, liver function testing

Approved in Japan as Indocyanine Green for:

• Diagnostic imaging agent for various medical procedures including sentinel lymph node mapping, liver function testing

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Findings from Research

Indocyanine green (ICG) was successfully used to detect sentinel lymph nodes in 150 out of 153 breast cancer patients, demonstrating a high sensitivity of 98.0%, which is better than traditional methods like radioisotope detection.

The specificity of ICG for sentinel lymph node detection was 100%, suggesting it is a highly reliable method, and the authors recommend its inclusion as a primary or alternative technique in clinical guidelines for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Indocyanine green in diagnostics and reconstructive surgery for breast cancer]. Zikiryakhodzhaev, AD., Starkov, MV., Timoshkin, VO.[2023]

Indocyanine green (ICG) fluorescence imaging demonstrated a high sentinel lymph node (SLN) detection rate of 98% in a study of 100 patients undergoing robotic-assisted hysterectomy for endometrial cancer, indicating its efficacy in improving surgical outcomes.

The use of ICG for SLN mapping is safe and effective, allowing for bilateral detection in 92% of cases and reducing the need for complete lymphadenectomy, which can lower morbidity and operative costs while still providing important staging information.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sentinel node mapping using indocyanine green and near-infrared fluorescence imaging technology for endometrial cancer: A prospective study using a surgical algorithm in Indian patients. Somashekhar, SP., Arvind, R., Kumar, CR., et al.[2022]

Indocyanine green (ICG) fluorescence-guided surgery enhances real-time visualization of anatomical structures, making it a promising innovation in surgical procedures.

ICG is currently used in various applications, including fluorescence cholangiography, bowel perfusion assessment, and tumor localization in oncological surgery, indicating its versatility and potential to improve surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of indocyanine green (ICG)-guided surgery in clinical practice: lesson to learn from other organs-an overview on clinical applications and future perspectives. Cassinotti, E., Boni, L., Baldari, L.[2023]

In a study of 102 patients undergoing laparoscopic total gastrectomy for cancer, the use of indocyanine green (ICG) fluorescence significantly increased the number of lymph nodes retrieved during surgery, with a median of 44 nodes compared to 32 nodes without ICG guidance.

ICG guidance was identified as the only independent factor positively influencing lymph node harvest, although its effectiveness was reduced in patients who had undergone neoadjuvant therapy or had positive lymph nodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Applicative Limitations of Indocyanine Green Fluorescence Assistance to Laparoscopic Lymph Node Dissection in Total Gastrectomy for Cancer. Puccetti, F., Cinelli, L., Genova, L., et al.[2022]

Indocyanine green (ICG) is increasingly used in colorectal surgery for its ability to enhance intraoperative visualization, including fluorescence angiography and detection of lymph node involvement, which improves surgical outcomes.

The use of ICG with near-infrared light provides detailed anatomical and functional information, leading to safer tumor removal and better preservation of surrounding structures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indocyanine Green (ICG) and Colorectal Surgery: A Literature Review on Qualitative and Quantitative Methods of Usage. Simion, L., Ionescu, S., Chitoran, E., et al.[2023]

In a study of 122 patients with gastric cancer, those who underwent indocyanine green (ICG)-guided laparoscopic radical gastrectomy had a significantly higher number of lymph nodes retrieved compared to those who did not use ICG, indicating improved surgical outcomes.

The study found no significant differences in perioperative, short-term, or long-term complications between the ICG and non-ICG groups, suggesting that ICG-guided surgery is both safe and effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The short-term and long-term outcomes of indocyanine green tracer-guided laparoscopic radical gastrectomy in patients with gastric cancer. Lu, X., Liu, S., Xia, X., et al.[2021]

A 76-year-old woman experienced severe hemodynamic instability during coronary artery bypass surgery after receiving indocyanine green (ICG) to check graft patency, highlighting potential adverse effects of ICG.

The case emphasizes the need for careful monitoring of blood pressure and heart rate during ICG administration, as well as the importance of having emergency measures ready to address any severe reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe hemodynamic instability after indocyanine green injection during off-pump coronary artery bypass grafting: A case report. Zhai, Q., Wang, Y., Tian, A.[2022]

In a study of 1414 patients undergoing sentinel lymph node biopsy for endometrial cancer, there were no reported anaphylactic reactions to indocyanine green (ICG), even among those with a history of iodine or contrast allergies.

The incidence of adverse reactions was low, with only 3 patients experiencing potentially allergic reactions, suggesting that ICG is safe for use in this context, especially when premedication with corticosteroids is applied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sentinel lymph node biopsy in patients with endometrial cancer and an indocyanine green or iodinated contrast reaction - A proposed management algorithm. Zammarrelli, WA., Afonso, AM., Broach, V., et al.[2022]

Indocyanine green (ICG) demonstrated a 99% identification rate for sentinel lymph nodes (SLN) in breast cancer patients, which is significantly higher than the 92.8% rate achieved with methylene blue (MB), indicating its superior efficacy as a tracer.

The study, involving 194 patients over a median follow-up of 67 months, found no allergic reactions or permanent skin staining related to ICG, suggesting it is a safe alternative to traditional SLN tracers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term and long-term outcomes of indocyanine green for sentinel lymph node biopsy in early-stage breast cancer. Hua, B., Li, Y., Yang, X., et al.[2022]

In a study of 23 patients undergoing soft-tissue sarcoma resection, ICG angiography demonstrated a high specificity (100%) and positive predictive value (100%) for predicting postoperative wound complications, particularly in the lower extremity.

The sensitivity of ICG angiography was lower at 50%, indicating that while it is very accurate when it predicts complications, it may miss some cases, especially in areas other than the lower extremity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative Indocyanine Green Fluorescence Angiography Is Sensitive for Predicting Postoperative Wound Complications in Soft-Tissue Sarcoma Surgery. Wilke, BK., Schultz, DS., Huayllani, MT., et al.[2021]

Indocyanine green (ICG) fluorescence was successfully used in a laparoscopic lymph node biopsy to visualize and detect pathologic lymph nodes in a patient with suspected lymphoma, demonstrating its potential as a safe and effective method for this purpose.

The case highlights that ICG fluorescence can enhance the identification of lymphomatous tissue during surgery, suggesting a novel application that warrants further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laparoscopic lymph node biopsy for lymphoma with a novel use of indocyanine green fluorescence in a 66-year-old male patient. Casaccia, M., Mora, M., Santori, G., et al.[2022]

Indocyanine green (ICG) imaging is a safe and cost-effective tool in colorectal surgery, particularly useful for assessing blood flow (perfusion) and potentially reducing complications like anastomotic leaks.

Current studies indicate promising applications of ICG for various purposes, including lymphatic mapping and identifying ureters, although more research is needed to strengthen the evidence base for its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indocyanine Green Fluorescence Guided Surgery in Colorectal Surgery. Garoufalia, Z., Wexner, SD.[2023]

Indocyanine green (ICG) is a fluorescent dye used in various surgical applications, including identifying sentinel lymph nodes and assessing skin perfusion during breast surgeries, highlighting its role in improving surgical outcomes.

ICG's ability to emit fluorescence when illuminated by near-infrared light allows for precise mapping of lymphatic networks and guidance in excising nonpalpable breast cancer, demonstrating its efficacy in oncological and reconstructive procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of indocyanine green angiography in oncological and reconstructive breast surgery]. Struk, S., Honart, JF., Qassemyar, Q., et al.[2018]

In a study of 34 patients with gastric cancer, those who underwent indocyanine green (ICG) guided lymphadenectomy removed significantly more lymph nodes (42) compared to those who had traditional surgery (28), suggesting improved surgical efficacy.

The ICG technique also identified a higher percentage of positive nodes for adenocarcinoma (10.6% in ICG positive nodes) compared to non-ICG nodes (1.9%), indicating its potential to enhance detection of cancer spread.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective cohort study of laparoscopic ICG-Guided Lymphadenectomy in gastric cancer from a Western country center. Maruri, I., Pardellas, MH., Cano-Valderrama, O., et al.[2023]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Indocyanine green in diagnostics and reconstructive surgery for breast cancer]. [2023]

2. India pubmed.ncbi.nlm.nih.gov

Sentinel node mapping using indocyanine green and near-infrared fluorescence imaging technology for endometrial cancer: A prospective study using a surgical algorithm in Indian patients. [2022]

3. Italy pubmed.ncbi.nlm.nih.gov

Application of indocyanine green (ICG)-guided surgery in clinical practice: lesson to learn from other organs-an overview on clinical applications and future perspectives. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Applicative Limitations of Indocyanine Green Fluorescence Assistance to Laparoscopic Lymph Node Dissection in Total Gastrectomy for Cancer. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Indocyanine Green (ICG) and Colorectal Surgery: A Literature Review on Qualitative and Quantitative Methods of Usage. [2023]

6. England pubmed.ncbi.nlm.nih.gov

The short-term and long-term outcomes of indocyanine green tracer-guided laparoscopic radical gastrectomy in patients with gastric cancer. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Severe hemodynamic instability after indocyanine green injection during off-pump coronary artery bypass grafting: A case report. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Sentinel lymph node biopsy in patients with endometrial cancer and an indocyanine green or iodinated contrast reaction - A proposed management algorithm. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Short-term and long-term outcomes of indocyanine green for sentinel lymph node biopsy in early-stage breast cancer. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Intraoperative Indocyanine Green Fluorescence Angiography Is Sensitive for Predicting Postoperative Wound Complications in Soft-Tissue Sarcoma Surgery. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Laparoscopic lymph node biopsy for lymphoma with a novel use of indocyanine green fluorescence in a 66-year-old male patient. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Indocyanine Green Fluorescence Guided Surgery in Colorectal Surgery. [2023]

13. France pubmed.ncbi.nlm.nih.gov

[Use of indocyanine green angiography in oncological and reconstructive breast surgery]. [2018]

14. Germany pubmed.ncbi.nlm.nih.gov

Retrospective cohort study of laparoscopic ICG-Guided Lymphadenectomy in gastric cancer from a Western country center. [2023]