Carbon Nanoparticles and Indocyanine Green for Sentinel Lymph Node Biopsy in Early Stage Cervical Cancer

December 7, 2021 updated by: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

A Randomized Controlled Comparison Study of Carbon Nanoparticles and Indocyanine Green for Sentinel Lymph Node Biopsy in Early Stage Cervical Cancer

The metastasis rate of pelvic lymph node in early cervical cancer is low. Systemic lymph node resection is traumatic and has many complications. Sentinel lymph node (SLN) biopsy can effectively avoid unnecessary lymph node dissection, which has been recommended in clinical guidelines. Indocyanine green(ICG) fluorescence imaging as the method of SLN mapping is recommended in international guidelines. However, the imaging equipment is very expensive which limits the popularization of ICG in different medical centers of various surgical volumes. Carbon nanoparticle is an innovative tracer without any special imaging equipment for SLN mapping in China. Some retrospective researches have proved that carbon nanoparticle is effective, simple, economic and suitable for popularization in different medical centers. In this study, a prospective randomized controlled trial will be conducted to analyze the non-inferiority of carbon nanoparticles compared to ICG, and to verify the application value of carbon nanoparticles. 144 cervical cancer patients with stage IB1 (FIGO2018) will be prospectively enrolled and randomly divided into two groups (R = 1:1). 72 patients will undergo SLN biopsy with carbon nanoparticles and 72 patients will be mapped by ICG. The primary endpoint is overall SLN detection rate. The secondary endpoints include bilateral SLN detection rate, the number of SLN detected, sensitivity, false negative rate and negative predictive value of SLN biopsy. Diagnostic accuracy will be evaluated at both pelvis and patient levels. What's more, SLN pathological ultrastaging will be conducted to increase the diagnostic accuracy. The hypothesis of this study is that the overall SLN detection rate by carbon nanoparticles is not inferior to that using ICG. And the differences of bilateral SLN detection rate, sensitivity, false negative rate and negative predictive value between two groups are not significant.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a prospective randomized controlled non-inferiority trial. Patients with early stage cervical cancer who met the inclusion criteria are divided into carbon nanoparticle group and ICG group by block random method. It is assumed that the overall SLN detection rate was PT (90%) in experimental group(carbon nanoparticle) and was PC (85%) in control group (ICG). The non-inferiority threshold Δ is -10%. The type I error and type II error of the hypothesis test are set as 0.05 and 0.2 respectively. The sample size is 60 cases in each group calculated by"Non inferiority tests for two proportions"method of Power Analysis and Sample Size (PASS) Software 11.0. After calculation, considering the 20% shedding rate, the sample size is 144 totally. There are 72 cases in experimental group and 72 cases in control group. Radical hysterectomy and systemic pelvic lymph node dissection are conducted after SLN resection, and paraaortic lymph node biopsy is conducted when necessary. Sentinel lymph nodes will be cut at 2-mm intervals perpendicular to the long axis in a bread-loaf fashion. Sentinel lymph nodes are then fixed in formalin and embedded in paraffin. Routine hemotoxin & eosin(H&E) staining is used for each SLN. Subsequent ultrastaging is performed if the initial H&E assessment is negative. SLN ultrastaging is performed by cutting three 5-μm sections at two levels, 50-μm apart, from each paraffin block of negative SLN. At the first level, two adjacent 5-μm sections are stained with H&E and immuno-histochemistry using the anti-cytokeratin AE1:AE3, respectively. At the second level, one 5-μm section is evaluated by H&E staining. Nonsentinel lymph nodes are bisected parallel to the long axis and stained with H&E staining.Nodal metastases are classified as (1) isolated tumor cells (ITCs) (single cells or clusters ≤ 0.2mm in largest dimension),(2) micrometastases (tumor deposits 0.2mm-2 mm), or (3) macrometastases (tumor deposits > 2mm). All pathological reviews will be finished by two independent gynecologic pathologists in the Department of Pathology of Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College. A third senior pathologist is invited to decide the diagnosis when discordance occurs.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
144

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100021
        • Department of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
        • Contact:
        • Principal Investigator:
          • Bin Li, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Cervical squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma diagnosed by pathological biopsy;
  • Tumor stage is IB1 (FIGO 2018);
  • No distant metastasis (chest, abdominal and pelvic enhanced CT or positron emission tomography (PET) -CT);
  • 18-70 years old;
  • Eastern Cooperative Oncology Group (ECOG) score ≤ 2 and tolerable for radical hysterectomy and systemic lymph node resection;
  • No obvious dysfunction or chronic disease of heart, liver and kidney, and no history of other malignant tumors;
  • Volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

  • Residual cervical cancer;
  • Small cell carcinoma, neuroendocrine carcinoma and other special histological types;
  • Patients who have received radiotherapy or chemotherapy before enrollment;
  • Allergic constitution, allergic to iodine;
  • ICG skin test is positive;
  • Patients considered unsuitable for inclusion by the researchers.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Carbon nanoparticles group
Procedure: Carbon nanoparticles
After pneumoperitoneum is established and laparoscopic instruments are prepared, according to National Comprehensive Cancer Network (NCCN) guidelines, 1ml diluted ICG solution (25 mg /10 ml) is injected into the submucosa around tumor at 3 and 9 o'clock of the cervix (2ml totally) with 1ml syringe. ICG should be slowly injected to avoid drug leakage. Intratumoral and deep cervical stroma injection should be avoided. The retroperitoneum is dissected immediately after injection under the multimodel observation of fluorescence laparoscopy. Search the fluorescent labeled lymphatics from bilateral parametrium to iliac vessels. The diffusion of ICG is rapid , and it is easy to spread to the next stations lymph nodes. The first fluorescent labeled lymph nodes on each lymphatic drainage pathway are identified as SLNs, other than all fluorescent lymph nodes. All detectable SLNs and enlarged or suspicious nodes regardless of mapping are resected for pathological examination alone.
Active Comparator: Indocyanine green group
Procedure: Indocyanine green
After pneumoperitoneum is established and laparoscopic instruments are prepared, according to NCCN guidelines, 0.5ml(25mg) carbon nanoparticle solution (the dose was from our retrospective study) is injected into the submucosa around tumor at 3 and 9 o'clock of the cervix (1ml totally) with 1ml syringe. Carbon nanoparticle should be slowly injected to avoid drug leakage. Intratumoral and deep cervical stroma injection should be avoided. The retroperitoneum is dissected immediately after injection. Search the black lymphatics from bilateral parametrium to iliac vessels. Because there is no fluorescence penetration as ICG, the black lymphatic vessels should be dissected carefully.The first black lymph nodes on each lymphatic drainage pathway are identified as SLNs, other than all black lymph nodes. All detectable SLNs and enlarged or suspicious nodes regardless of mapping are resected for pathological examination alone.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall SLN detection rate
Time Frame: From date of operation to the date of completion of routine pathological examination, usually 2 weeks after operation.
The percentage of patients with successfully detected SLNs in all eligible patients.
From date of operation to the date of completion of routine pathological examination, usually 2 weeks after operation.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Bilateral SLN detection rate
Time Frame: From date of operation to the date of completion of routine pathological examination, usually 2 weeks after operation.
The percentage of patients with successfully detected SLNs in both sides of the pelvis in all eligible patients
From date of operation to the date of completion of routine pathological examination, usually 2 weeks after operation.
The number of detected SLNs
Time Frame: From date of operation to the date of completion of routine pathological examination, usually 2 weeks after operation.
The numbers of detected SLNs are calculated by the pathologist.
From date of operation to the date of completion of routine pathological examination, usually 2 weeks after operation.
Location of SLNs
Time Frame: From date of operation to the date of completion of routine pathological examination, usually 2 weeks after operation.
Distribution of SLNs in pelvic and abdominal cavity, including external iliac, obturator fossa, internal ilia, deep inguinal, common iliac, presacral, inferior vena cava, para-aortic, and parametrial regions.
From date of operation to the date of completion of routine pathological examination, usually 2 weeks after operation.
Sensitivity of SLN biopsy
Time Frame: From date of operation to the date of completion of SLNs pathological ultrastaging. 3 years.
The percentage of patients or pelvises with positive SLNs in pathological examination among those with positive pelvic lymph nodes.
From date of operation to the date of completion of SLNs pathological ultrastaging. 3 years.
False negative rate
Time Frame: From date of operation to the date of completion of SLNs pathological ultrastaging. 3 years.
The percentage of patients or pelvises with negative SLNs in pathological examination among those with positive pelvic lymph nodes.
From date of operation to the date of completion of SLNs pathological ultrastaging. 3 years.
Negative predictive value
Time Frame: From date of operation to the date of completion of SLNs pathological ultrastaging. 3 years.
The percentage of patients or pelvises with negative pelvic lymph nodes among those whose SLNs were negative in pathological examination.
From date of operation to the date of completion of SLNs pathological ultrastaging. 3 years.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Duration of operation
Time Frame: One month.
The time from the beginning of the operation to the end of the operation.
One month.
Intraoperative bleeding volume
Time Frame: One month.
The amount of bleeding during the operation.
One month.
Adverse events caused by injection of tracers.
Time Frame: From the time of tracer injection to the date of leaving hospital.
Adverse events, such as allergy, are caused by injection of tracers and defined according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
From the time of tracer injection to the date of leaving hospital.
Operative complications
Time Frame: From the beginning of operation to 6 months after operation.
In this study, operative complications are defined according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
From the beginning of operation to 6 months after operation.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Bin Li, M.D., Department of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2022

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 15, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 7, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 22, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 22, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 7, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CFH2020-2-4024

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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