Fluorescence Targeted Pelvic Lymph Node Mapping

NCT ID: NCT03204994

Last Updated: 2019-08-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-01
• Study Completion Date: 2018-08-01

Brief Summary

This study aims to assess the lymphatic drainage of rectal tumours by using ICG as a fluorescent non-specific marker. As a feasibility study, it will also assess its technique and timing along with its ability to assist in removing lymph nodes when it is clinically indicated.

Detailed Description

Current surgical treatment for rectal cancer includes total mesorectal excision (TME) which involves excision of the rectum in its encompassing fat including the lymph nodes. Rectal cancer can spread to lymph nodes locally inside the TME 'package' and the lateral pelvic lymph nodes. The TME must be fully excised to ensure that the circumferential resection margin (CRM) is disease free or negative. Despite advancing surgical techniques, a positive margin can occur in around 9% of patients with accurate pre-operative magnetic resonance imaging (MRI), increasing the risk of local recurrence.

Incidence of lateral pelvic lymph node involvement has been reported between 10-25%. It is thought that lower rectal tumours are more likely to spread to the lateral pelvic nodes. In the far East, LPLN dissection is often added to the TME procedure. Formal LPLND is not utilised in Europe due to operative risks including damage to pelvic nerves, greater blood loss and prolonged operating time. Instead, neoadjuvant chemoradiotherapy (CRT) is utilised to 'sterilise' the lymph nodes. Although a retrospective analysis suggested that LPLN dissection is equivalent to preoperative CRT for preventing local recurrence, there has been evidence to suggest that positive LPLNs after CRT decrease cancer specific survival and relapse free survival. This would suggest that there may be a cohort of patients that would benefit from some form of LPLN dissection, although it is not certain what characteristics of tumours are more likely to metastasise to the LPLNs.

In prostatectomies, where pelvic lymph node dissection is a standard part of the procedure, there has been investigation into fluorescence guided lymph node mapping. Yuen et al utilised ICG guided node mapping in open prostatectomy. In their study, all lymph nodes identified by fluorescence were found to have metastases on pathology whereas non-fluorescent nodes were free from disease. A smaller, retrospective study comparing fluorescence guided lymph node dissection with standard lymph node dissection showed higher sensitivity and specificity in the fluorescence guided technique. Similar results were seen in an early, robotic prostatectomy study.

ICG has been used to map pelvic lymph nodes in colorectal cancer, with the first reported cases being published in 2010. ICG was injected to the tumour base in 25 open rectal resections. A wide field camera is useful for fluorescence in open surgery, however, as most rectal cancer cases are performed using a minimally invasive approach a laparoscopic method is needed. Ishizuka et al used a similar method in low rectal cancers to identify drainage in three different sets of lymph nodes. In 2015, a study of 5 patients using ICG node mapping with the same laparoscopic equipment to be used in this study demonstrated fluorescence in all 5 patients. Both studies 'berry picked' the fluorescing lymph nodes. In the 2010 study, 23 out of 25 patients had fluorescing lymph nodes. In the 2 non-fluorescing nodes LPLD was performed and no diseased nodes were identified. In these studies, they did not observe what types of tumours drain to the LPLDs.

ICG, when injected intravenously, rapidly binds to plasma proteins and is exclusively excreted into bile by the liver. It is known to be well tolerated but there have been reported cases of urticaria and anaphylaxis. Risk of anaphylaxis is 1 in 10,000 and if occurs can be treated using a standard protocol. ICG contains sodium iodide and therefore should be avoided in patients with known allergy to iodides.

This study aims to assess the lymphatic drainage of rectal tumours by using ICG as a fluorescent non-specific marker. As a feasibility study, it will also assess its technique and timing along with its ability to assist in removing lymph nodes when it is clinically indicated.

Conditions

Cancer of Rectum; Lymph Node Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tumour injection of ICG

Indocyanine green injection into tumour before or during surgery.

Group Type: EXPERIMENTAL

Indocyanine Green

Intervention Type: DRUG

Fluorescence guided lymphatic mapping using indocyanine green.

Interventions

Indocyanine Green

Fluorescence guided lymphatic mapping using indocyanine green.

Intervention Type: DRUG

Other Intervention Names

ICG

Eligibility Criteria

Inclusion Criteria

• Participant is willing and able to give informed consent for participation in the study.
• Male or Female, aged 18 years or above.
• Participant is undergoing elective curative surgery for rectal adenocarcinoma
• Participant is willing and able to comply with study requirements

Exclusion Criteria

• Participant has history of or known allergy to indocyanine green
• Participant has history of or known allergy to iodides
• Participant suffers from hyperthyroidism or has a benign thyroid tumour
• Participant has renal failure
• Female participant currently pregnant, planning pregnancy or breast feeding

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Oxford University Hospitals NHS Trust

OTHER

Sponsor Role: lead

Responsible Party

Thomas Barnes

Clinical Research Fellow

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Chris Cunningham, MD

Role: PRINCIPAL_INVESTIGATOR

Chief Investigator

Thomas Barnes, MBChB

Role: PRINCIPAL_INVESTIGATOR

Clinical Research Fellow

Locations

Oxford University Hospitals NHS Foundation Trust

Oxford, Oxfordshire, United Kingdom

Countries

United Kingdom

Other Identifiers

12451

Identifier Type: -

Identifier Source: org_study_id