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

NCT05167149 | Unknown

• 1 other identifier: CFH2020-2-4024
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cervical Cancer Stage IB1

Keywords

Early Stage Cervical Cancer; Sentinel Lymph Node Biopsy; Carbon Nanoparticle; Indocyanine Green; Ultrastaging

Outcome Measures

Primary Outcomes (1)

• Overall SLN detection rate

  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 Outcomes (6)

• Bilateral SLN detection rate

  From date of operation to the date of completion of routine pathological examination, usually 2 weeks after operation.

• The number of detected SLNs

  From date of operation to the date of completion of routine pathological examination, usually 2 weeks after operation.

• Location of SLNs

  From date of operation to the date of completion of routine pathological examination, usually 2 weeks after operation.

• Sensitivity of SLN biopsy

  From date of operation to the date of completion of SLNs pathological ultrastaging. 3 years.

• False negative rate

  From date of operation to the date of completion of SLNs pathological ultrastaging. 3 years.

Other Outcomes (4)

• Duration of operation

  One month.

• Intraoperative bleeding volume

  One month.

• Adverse events caused by injection of tracers.

  From the time of tracer injection to the date of leaving hospital.

Study Arms (2)

Carbon nanoparticles group

EXPERIMENTAL

Procedure: Carbon nanoparticles

Indocyanine green group

ACTIVE COMPARATOR

Procedure: Indocyanine green

Interventions

Carbon nanoparticles PROCEDURE

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.

Carbon nanoparticles group

Indocyanine green PROCEDURE

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.

Indocyanine green group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

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

Beijing, Beijing Municipality, 100021, China

Location

Related Publications (10)

• Cibula D, Dusek J, Jarkovsky J, Dundr P, Querleu D, van der Zee A, Kucukmetin A, Kocian R. A prospective multicenter trial on sentinel lymph node biopsy in patients with early-stage cervical cancer (SENTIX). Int J Gynecol Cancer. 2019 Jan;29(1):212-215. doi: 10.1136/ijgc-2018-000010.

  PMID: 30640706 BACKGROUND

• Cibula D, McCluggage WG. Sentinel lymph node (SLN) concept in cervical cancer: Current limitations and unanswered questions. Gynecol Oncol. 2019 Jan;152(1):202-207. doi: 10.1016/j.ygyno.2018.10.007. Epub 2018 Oct 11.

  PMID: 30318103 BACKGROUND

• Frumovitz M, Plante M, Lee PS, Sandadi S, Lilja JF, Escobar PF, Gien LT, Urbauer DL, Abu-Rustum NR. Near-infrared fluorescence for detection of sentinel lymph nodes in women with cervical and uterine cancers (FILM): a randomised, phase 3, multicentre, non-inferiority trial. Lancet Oncol. 2018 Oct;19(10):1394-1403. doi: 10.1016/S1470-2045(18)30448-0. Epub 2018 Aug 22.

  PMID: 30143441 BACKGROUND

• Salvo G, Ramirez PT, Levenback CF, Munsell MF, Euscher ED, Soliman PT, Frumovitz M. Sensitivity and negative predictive value for sentinel lymph node biopsy in women with early-stage cervical cancer. Gynecol Oncol. 2017 Apr;145(1):96-101. doi: 10.1016/j.ygyno.2017.02.005. Epub 2017 Feb 8.

  PMID: 28188015 BACKGROUND

• Buda A, Crivellaro C, Elisei F, Di Martino G, Guerra L, De Ponti E, Cuzzocrea M, Giuliani D, Sina F, Magni S, Landoni C, Milani R. Impact of Indocyanine Green for Sentinel Lymph Node Mapping in Early Stage Endometrial and Cervical Cancer: Comparison with Conventional Radiotracer (99m)Tc and/or Blue Dye. Ann Surg Oncol. 2016 Jul;23(7):2183-91. doi: 10.1245/s10434-015-5022-1. Epub 2015 Dec 29.

  PMID: 26714944 BACKGROUND

• Bats AS, Frati A, Mathevet P, Orliaguet I, Querleu D, Zerdoud S, Leblanc E, Gauthier H, Uzan C, Deandreis D, Darai E, Kerrou K, Marret H, Lenain E, Froissart M, Lecuru F. Contribution of lymphoscintigraphy to intraoperative sentinel lymph node detection in early cervical cancer: Analysis of the prospective multicenter SENTICOL cohort. Gynecol Oncol. 2015 May;137(2):264-9. doi: 10.1016/j.ygyno.2015.02.018. Epub 2015 Feb 26.

  PMID: 25727652 BACKGROUND

• Imboden S, Papadia A, Nauwerk M, McKinnon B, Kollmann Z, Mohr S, Lanz S, Mueller MD. A Comparison of Radiocolloid and Indocyanine Green Fluorescence Imaging, Sentinel Lymph Node Mapping in Patients with Cervical Cancer Undergoing Laparoscopic Surgery. Ann Surg Oncol. 2015 Dec;22(13):4198-203. doi: 10.1245/s10434-015-4701-2. Epub 2015 Jun 30.

  PMID: 26122376 BACKGROUND

• Zuo J, Wu LY, Cheng M, Bai P, Lei CZ, Li N, Zhang GY, Zhao D, Li B. Comparison Study of Laparoscopic Sentinel Lymph Node Mapping in Endometrial Carcinoma Using Carbon Nanoparticles and Lymphatic Pathway Verification. J Minim Invasive Gynecol. 2019 Sep-Oct;26(6):1125-1132. doi: 10.1016/j.jmig.2018.11.002. Epub 2018 Nov 14.

  PMID: 30445188 BACKGROUND

• Kim CH, Soslow RA, Park KJ, Barber EL, Khoury-Collado F, Barlin JN, Sonoda Y, Hensley ML, Barakat RR, Abu-Rustum NR. Pathologic ultrastaging improves micrometastasis detection in sentinel lymph nodes during endometrial cancer staging. Int J Gynecol Cancer. 2013 Jun;23(5):964-70. doi: 10.1097/IGC.0b013e3182954da8.

  PMID: 23694985 BACKGROUND

• Cusimano MC, Vicus D, Pulman K, Maganti M, Bernardini MQ, Bouchard-Fortier G, Laframboise S, May T, Hogen LF, Covens AL, Gien LT, Kupets R, Rouzbahman M, Clarke BA, Mirkovic J, Cesari M, Turashvili G, Zia A, Ene GEV, Ferguson SE. Assessment of Sentinel Lymph Node Biopsy vs Lymphadenectomy for Intermediate- and High-Grade Endometrial Cancer Staging. JAMA Surg. 2021 Feb 1;156(2):157-164. doi: 10.1001/jamasurg.2020.5060.

  PMID: 33175109 BACKGROUND

Related Links

• Clinical analysis of 76 cases of sentinel lymph node detection in cervical cancer and endometrial cancer

MeSH Terms

Interventions

Indocyanine Green

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• 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

  STUDY CHAIR

Central Study Contacts

Bin Li, M.D.

CONTACT

+86 13801364117; libin@cicams.ac.cn

Hongyi Hou, M.D.

CONTACT

+86 13031191717; cdhhongyi@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2021
• First Posted: December 22, 2021
• Study Start: February 1, 2022
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: December 22, 2021

Record last verified: 2021-01

Locations

CN (1)