Carbon Nanoparticles as Lymph Node Tracer in Rectal Cancer After Neoadjuvant Radiochemotherapy

Rectal Cancer Clinical Trial

— CALOR-NAT  

Official title:

Prospective Randomized Clinical Trial of Carbon Nanoparticles as Lymph Node Tracer in Rectal Cancer After Neoadjuvant Radiochemotherapy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03550001
• Other study ID #: 2017-PKUPH077
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2018
• Est. completion date: October 1, 2023

Study information

• Verified date: May 2018
• Source: Peking University People's Hospital
• Contact: Yingjiang Ye, MD,PhD
• Phone: 8610-88326608
• Email: yeyingjiang[@]pkuph.edu.cn, yjye101[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate whether injection of carbon nanoparticle as a lymph node tracer before neoadjuvant radiochemotherapy in rectal cancer can increase lymph node yield after surgery compared which do not inject.

Description:

This is the randomized controlled, multi-centers，and open-labeled study. The lymph node yield was significantly decreased in rectal cancer after neoadjuvant radiochemotherapy (NAT), hard for pathologists to detect, and is difficult to meet the guideline that minimun of 12 lymph nodes should be retrived after surgery in colorectal cancer. Carbon nanoparticle (CNP) is a specific lymph node tracer, which only dyeing the lymph node, and can keep the lymph node in dyeing state in at least half year. The inverstigator attempted to compare the amount of lymph node yield after surgery in locally advanced rectal caner between injection CNP before NAT and no injection CNP before NAT. In this study, the participants with clinical TNM stage T3+ or N+ will be recruited. The participants will be randomized (1:1 ratio) to a control and intervention arm. The participants in the control arm will not receive injection of any kind lymph node tracers. The participants in the intervention arm will receive injection of CNP before NAT. And the specimen would be evaluated by the pathologist.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 252
• Est. completion date: October 1, 2023
• Est. primary completion date: June 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age: 18-75 years old;

2. Histologically confirmed adenocarcinoma;

3. The rectal adenocarcinoma 0-12cm from the anal margin;

4. Clinical TNM stage: T3+ or N+;

5. Untreated patients (who have not received treatment including radiotherapy, chemotherapy, and surgery);

6. Good liver and kidney function, without contraindications for radiotherapy, chemotherapy or surgery;

7. Able and willing to give informed consent to participate;

Exclusion Criteria:

1. Malignant tumor history or other malignant tumors;

2. Emergency operations such as intestinal obstruction, perforation and hemorrhage;

3. Pregnant or lactating women;

4. History of severe mental illness;

5. Contraindications for radiotherapy, chemotherapy and surgery;

6. Conditions that the researcher thinks it is not suitable for selection.

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Procedure:
• Injection CNP before NAT
Injection carbon nanoparticle via rectal mucosa before neoadjuvant therapy

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
YE Yingjiang

References & Publications (17)

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Carvalho C, Glynne-Jones R. Challenges behind proving efficacy of adjuvant chemotherapy after preoperative chemoradiation for rectal cancer. Lancet Oncol. 2017 Jun;18(6):e354-e363. doi: 10.1016/S1470-2045(17)30346-7. Review. Erratum in: Lancet Oncol. 2018 Mar;19(3):e137. — View Citation

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Farinella E, Viganò L, Fava MC, Mineccia M, Bertolino F, Capussotti L. In vivo lymph node mapping and pattern of metastasis spread in locally advanced mid/low rectal cancer after neoadjuvant chemoradiotherapy. Int J Colorectal Dis. 2013 Nov;28(11):1523-9. doi: 10.1007/s00384-013-1727-4. Epub 2013 Jul 23. — View Citation

Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rödel C, Cervantes A, Arnold D; ESMO Guidelines Committee. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(suppl_4):iv22-iv40. doi: 10.1093/annonc/mdx224. — View Citation

Gurawalia J, Dev K, Nayak SP, Kurpad V, Pandey A. Less than 12 lymph nodes in the surgical specimen after neoadjuvant chemo-radiotherapy: an indicator of tumor regression in locally advanced rectal cancer? J Gastrointest Oncol. 2016 Dec;7(6):946-957. doi: 10.21037/jgo.2016.09.03. — View Citation

Horne J, Carr NJ, Bateman AC, Kandala N 2nd, Adams J, Silva S, Ryder I. A comparison of formalin and GEWF in fixation of colorectal carcinoma specimens: rates of lymph node retrieval and effect on TNM staging. J Clin Pathol. 2016 Jun;69(6):511-7. doi: 10.1136/jclinpath-2015-203281. Epub 2015 Nov 30. — View Citation

Kim HJ, Jo JS, Lee SY, Kim CH, Kim YJ, Kim HR. Low Lymph Node Retrieval After Preoperative Chemoradiation for Rectal Cancer is Associated with Improved Prognosis in Patients with a Good Tumor Response. Ann Surg Oncol. 2015;22(6):2075-81. doi: 10.1245/s10434-014-4235-z. Epub 2014 Nov 14. — View Citation

Lykke J, Jess P, Roikjaer O; Danish Colorectal Cancer Group. A minimum yield of twelve lymph nodes in rectal cancer remains valid in the era of neo-adjuvant treatment : results from a national cohort study. Int J Colorectal Dis. 2015 Mar;30(3):347-51. doi: 10.1007/s00384-015-2145-6. Epub 2015 Feb 5. — View Citation

Lykke J, Jess P, Roikjaer O; Danish Colorectal Cancer Group. Increased Lymph Node Yield Is Associated With Improved Survival in Rectal Cancer Irrespective of Neoadjuvant Treatment: Results From a National Cohort Study. Dis Colon Rectum. 2015 Sep;58(9):823-30. doi: 10.1097/DCR.0000000000000429. — View Citation

Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, Roussel A, Jacob JH, Segol P, Samama G, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994 Jun 1;73(11):2680-6. — View Citation

Mechera R, Schuster T, Rosenberg R, Speich B. Lymph node yield after rectal resection in patients treated with neoadjuvant radiation for rectal cancer: A systematic review and meta-analysis. Eur J Cancer. 2017 Feb;72:84-94. doi: 10.1016/j.ejca.2016.10.031. Epub 2016 Dec 24. Review. — View Citation

Münster M, Hanisch U, Tuffaha M, Kube R, Ptok H. Ex Vivo Intra-arterial Methylene Blue Injection in Rectal Cancer Specimens Increases the Lymph-Node Harvest, Especially After Preoperative Radiation. World J Surg. 2016 Feb;40(2):463-70. doi: 10.1007/s00268-015-3230-2. — View Citation

Wang Y, Deng H, Chen H, Liu H, Xue Q, Yan J, Li G. Preoperative Submucosal Injection of Carbon Nanoparticles Improves Lymph Node Staging Accuracy in Rectal Cancer after Neoadjuvant Chemoradiotherapy. J Am Coll Surg. 2015 Nov;221(5):923-30. doi: 10.1016/j.jamcollsurg.2015.07.455. Epub 2015 Aug 20. — View Citation

Xu Z, Berho ME, Becerra AZ, Aquina CT, Hensley BJ, Arsalanizadeh R, Noyes K, Monson JRT, Fleming FJ. Lymph node yield is an independent predictor of survival in rectal cancer regardless of receipt of neoadjuvant therapy. J Clin Pathol. 2017 Jul;70(7):584-592. doi: 10.1136/jclinpath-2016-203995. Epub 2016 Dec 8. — View Citation

Yegen G, Keskin M, Büyük M, Kunduz E, Balik E, Saglam EK, Kapran Y, Asoglu O, Güllüoglu M. The effect of neoadjuvant therapy on the size, number, and distribution of mesorectal lymph nodes. Ann Diagn Pathol. 2016 Feb;20:29-35. doi: 10.1016/j.anndiagpath.2015.10.008. Epub 2015 Oct 29. — View Citation

Zhang XM, Liang JW, Wang Z, Kou JT, Zhou ZX. Effect of preoperative injection of carbon nanoparticle suspension on the outcomes of selected patients with mid-low rectal cancer. Chin J Cancer. 2016 Apr 4;35:33. doi: 10.1186/s40880-016-0097-z. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	lymph node yield	Amount of lymph node yield, dyeing lymph node, positive lymph node and the dyeing positive lymph node	up to 30days after total mesorectal excision
Secondary	Impact on surgical operations	The impact of CNP to operational level	Time of surgery
Secondary	Quality of surgery	Quality of surgery determined using the mesorectal grading system	Time of surgery
Secondary	Surgery morbidity	Surgical morbidity reported according to Clavien-Dindo classification	30 days and 12-months
Secondary	Overall survival	Overall Survival is defined as the time from the date of surgery to the date of death	5-years
Secondary	Disease free survival	Disease Free Survival is defined as the time from the date of surgery to the date of the local recurrence, and/or distant disease, or tumor-related death	5-years
Secondary	Local recurrence rate	Local recurrence rate is defined as the time from the date of surgery to the date of the local recurrence	5-years