Fluorescent Tumor Margin Examination for Sarcoma

(ICGTM Trial)

Recruiting at 1 trial location

Overseen By Beata Krawczyk, [e-mail]

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kurt Weiss

Disqualifiers: Pregnancy, Renal failure, Fluorescein allergy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

110 Participants Needed

Trial Summary

What is the purpose of this trial?

Tumor margin confirmation is important to confirming appropriate disease excision. Current standard of care is to take select margin samples to pathology for intra-operative readings. However, this is expensive, time consuming, and only assesses the margin contained within the specific sample. In prior work the investigators have determined that indocyanine green (ICG) is highly specific to the tumor bed when injected shortly before surgery. The investigators hypothesize that ICG will be able to accurately identify residual positive tumor margins during sarcoma excision procedures.

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) Fluorescence Imaging for tumor margin examination in sarcoma?

Research shows that Indocyanine Green (ICG) is effective in identifying sentinel lymph nodes in breast cancer and has been used in photodynamic therapy to inhibit cancer growth, suggesting its potential usefulness in tumor margin examination for sarcoma. ^{1 2 3 4 5}

Is Indocyanine Green (ICG) safe for use in humans?

Indocyanine Green (ICG) has been used safely in various medical procedures, such as sentinel lymph node mapping in breast and endometrial cancer, with no significant adverse reactions reported. Studies suggest it is generally safe for human use. ^{2 5 6 7 8}

How does the treatment using fluorescent tumor margin examination for sarcoma differ from other treatments?

This treatment uses indocyanine green (ICG), a fluorescent dye, to help surgeons see the edges of a tumor during surgery, which can improve the chances of removing the entire tumor and reduce the risk of it coming back. This approach is unique because it provides real-time visual guidance during surgery, unlike traditional methods that rely on post-surgery pathology results. ^{2 5 9 10 11}

Research Team

Kurt E Weiss

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for adults over 18 with primary musculoskeletal tumors scheduled for surgery. Candidates must have a tumor that hasn't been removed before and has a risk of coming back. It's not for those under 18, pregnant or breastfeeding women, people who've had previous surgery near the tumor, kidney failure patients, or anyone allergic to contrast media.

Inclusion Criteria

I gave my permission for surgery before agreeing to join the study.

I am over 18 and need surgery for a bone or muscle tumor.

My biopsy shows I have a primary soft tissue or bone tumor that hasn't been removed and could recur.

Exclusion Criteria

I have had surgery before on the area where my tumor is located.

You have had a severe allergic reaction to contrast media or fluorescein in the past.

My tumor has not or barely come back after treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Pre-operative

Participants receive ICG injection 2 hours prior to surgery

2 hours

1 visit (in-person)

Surgery

Tumor removal surgery with ICG angiography to detect residual tumor margins

1 day

1 visit (in-person)

Follow-up

Participants are monitored for tumor recurrence and compared with ICG angiography findings

2 years

Treatment Details

Interventions

• Indocyanine green solution administered at 2.0mg/kg.
• Indocyanine green solution administered at 2.5mg/kg.
• Stryker SPY-PHI Imaging Device

Trial Overview The study tests if injecting indocyanine green (ICG) can help surgeons see cancerous tissue edges during sarcoma removal surgeries better than current methods. The Stryker SPY-PHI Imaging Device will be used to visualize the ICG-stained tissues in real-time.

Participant Groups

Group I: ICG use followed by SPY-PHI imaging. Experimental Treatment 2 Interventions

Participants will be injected with 2.0mg/kg of ICG dye to access tumor margin using Stryker SPY imaging technology.

Who Is Running the Clinical Trial?

Kurt Weiss

Lead Sponsor

Trials

1

Recruited

110+

Stryker Nordic

Industry Sponsor

Trials

35

Recruited

4,400+

Findings from Research

Indocyanine green (ICG) photodynamic therapy (PDT) effectively induces cell death in pancreatic cancer cells, showing significant growth inhibition at doses as low as 10 microg/mL when combined with infrared light exposure.

The combination of ICG and infrared light resulted in nearly total ablation of cancer cells at 20 microg/mL, while neither ICG nor the laser alone caused toxicity, suggesting a promising treatment option with minimal side effects for patients with difficult-to-treat pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infrared laser activation of indocyanine green inhibits growth in human pancreatic cancer. Tseng, WW., Saxton, RE., Deganutti, A., et al.[2019]

In a study of 278 breast cancer patients, indocyanine green (IcG) was found to have a similar oncologic yield for sentinel lymph node mapping compared to isosulfan blue (IB), indicating that IcG is a viable alternative.

Although the operative time was longer for IcG compared to IB, the transition to using IcG can be done safely, suggesting that surgeons can adopt this method without compromising patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of learning curve with Indocyanine Green (IcG) versus blue dye for sentinel lymph node biopsy in breast cancer. Hounschell, CA., Kilgore, LJ., Pruitt, P., et al.[2023]

Indocyanine green (ICG) combined with diode laser treatment was effective in treating macular and plaque-type Kaposi sarcomas in 6 male patients, with 19 out of 27 lesions resolving completely and no recurrence over a 2-year follow-up.

The treatment had a low side effect profile, with only mild burning sensations reported during irradiation and some transient hyperpigmentation, indicating it is a safe option for palliative care in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Photochemotherapy of cutaneous AIDS-associated Kaposi sarcoma with indocyanine green and laser light]. Szeimies, RM., Lorenzen, T., Karrer, S., et al.[2019]

Indocyanine green angiography (ICGA) is a valuable adjunct to intravenous sodium fluorescein angiography (IVFA) for evaluating retinal disorders, particularly when choroidal pathology is suspected.

As technology advances, ICGA may become a more significant diagnostic tool, potentially helping to prevent severe vision loss from various retinal disorders, despite currently being secondary to IVFA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous and indocyanine green angiography. Dzurinko, VL., Gurwood, AS., Price, JR.[2022]

Indocyanine green (ICG) fluorescence imaging demonstrated a high sensitivity of 100% for sentinel lymph node (SLN) detection in early breast cancer, confirming its effectiveness when used alongside blue dye and radiocolloid.

The combination of ICG and blue dye provided the highest detection rate at 95%, suggesting a dual approach that could eliminate the need for radioisotope in SLN biopsies, enhancing safety and simplifying the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A feasibility study (ICG-10) of indocyanine green (ICG) fluorescence mapping for sentinel lymph node detection in early breast cancer. Wishart, GC., Loh, SW., Jones, L., et al.[2022]

The ICG Finger Monitor system accurately measures indocyanine green (ICG) concentrations in the blood, showing a strong correlation (r = 0.998) with plasma ICG levels in a range from 0.04 mg/dl to 1.0 mg/dl, making it a reliable tool for monitoring liver function.

In a study of 196 patients with chronic liver disease, the ICG Finger Monitor demonstrated significant differences in plasma disappearance rates and blood retention ratios between healthy controls and those with chronic hepatitis or cirrhosis, indicating its potential for clinical use in assessing liver health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of ICG Finger Monitor in patients with liver disease. Ishigami, Y., Masuzawa, M., Miyoshi, E., et al.[2019]

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) did not show toxicity to cultured ARPE19 cells at concentrations below 5 mg/ml and exposure times ranging from 2 minutes to 2 hours, indicating its safety for use in these conditions.

Older ARPE19 cell cultures (over 30 days) demonstrated greater resistance to hypotonic ICG solutions compared to younger cultures, suggesting that cell maturity may influence susceptibility to ICG toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An isotonic preparation of 1 mg/ml indocyanine green is not toxic to hyperconfluent ARPE19 cells, even after prolonged exposure. Kiilgaard, JF., Nissen, MH., la Cour, M.[2016]

In a study of 18 patients with soft tissue sarcomas, the use of indocyanine green (ICG) dye for intraoperative margin assessment showed that 56% of ICG margins matched permanent pathology results, indicating its potential effectiveness in achieving negative margins during surgery.

ICG demonstrated a high specificity of 89% for identifying tumor margins, suggesting it could be a valuable tool in sarcoma surgery, although further research with larger sample sizes is needed to optimize its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative Evaluation of Soft Tissue Sarcoma Surgical Margins with Indocyanine Green Fluorescence Imaging. Gong, MF., Li, WT., Bhogal, S., et al.[2023]

In a study involving 115 patients with intermediate to high-grade sarcomas, the use of indocyanine green (ICG) and near-infrared (NIR) fluorescence guidance during surgery significantly reduced the unexpected positive margin rate from 25.0% to 5.1%.

The majority of tumors (37 out of 39) in the ICG group fluoresced, and surgeons reported that the intra-operative imaging aided their decision-making in 11 cases, suggesting that ICG can effectively assist in achieving clearer surgical margins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative Near-Infrared Fluorescence Guided Surgery Using Indocyanine Green (ICG) for the Resection of Sarcomas May Reduce the Positive Margin Rate: An Extended Case Series. Brookes, MJ., Chan, CD., Nicoli, F., et al.[2021]

In a study of 714 patients with early breast cancer, the combination of indocyanine green (ICG) fluorescence and blue dye achieved a remarkable sentinel lymph node (SLN) detection rate of 99.6%, indicating its high efficacy for identifying lymph nodes during surgery.

The method demonstrated a low axillary lymph node recurrence rate of only 0.4% during a follow-up period of up to 87.7 months, suggesting it is a safe and effective alternative to traditional methods involving dye and radioisotope.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axillary lymph node recurrence after sentinel lymph node biopsy performed using a combination of indocyanine green fluorescence and the blue dye method in early breast cancer. Inoue, T., Nishi, T., Nakano, Y., et al.[2022]

References

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

Infrared laser activation of indocyanine green inhibits growth in human pancreatic cancer. [2019]

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

Evaluation of learning curve with Indocyanine Green (IcG) versus blue dye for sentinel lymph node biopsy in breast cancer. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

[Photochemotherapy of cutaneous AIDS-associated Kaposi sarcoma with indocyanine green and laser light]. [2019]

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

Intravenous and indocyanine green angiography. [2022]

5. England pubmed.ncbi.nlm.nih.gov

A feasibility study (ICG-10) of indocyanine green (ICG) fluorescence mapping for sentinel lymph node detection in early breast cancer. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical applications of ICG Finger Monitor in patients with liver disease. [2019]

7. 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]

8. Denmark pubmed.ncbi.nlm.nih.gov

An isotonic preparation of 1 mg/ml indocyanine green is not toxic to hyperconfluent ARPE19 cells, even after prolonged exposure. [2016]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Intraoperative Evaluation of Soft Tissue Sarcoma Surgical Margins with Indocyanine Green Fluorescence Imaging. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Intraoperative Near-Infrared Fluorescence Guided Surgery Using Indocyanine Green (ICG) for the Resection of Sarcomas May Reduce the Positive Margin Rate: An Extended Case Series. [2021]

11. Japan pubmed.ncbi.nlm.nih.gov

Axillary lymph node recurrence after sentinel lymph node biopsy performed using a combination of indocyanine green fluorescence and the blue dye method in early breast cancer. [2022]