Comparison of Hepatectomy and Local Ablation for Resectable Synchronous and Metachronous Colorectal Liver Metastasis

Secondary Malignant Neoplasm of Liver Clinical Trial

— HELARC  

Official title:

Comparison of Hepatectomy and Local Ablation for Resectable Synchronous and Metachronous Colorectal Liver Metastasis (HELARC) ------ a Randomized Controlled Multicenter Clinical Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02886104
• Other study ID #: E2016026
• Status: Recruiting
• Phase: N/A
• First received: August 24, 2016
• Last updated: August 28, 2016
• Start date: August 2016
• Est. completion date: July 2026

Study information

• Verified date: August 2016
• Source: Sixth Affiliated Hospital, Sun Yat-sen University
• Contact: Meijin Huang, MD,PHD
• Phone: +8613924073322
• Email: maymay0129[@]139.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The surgical and local ablation strategy for the treatment of resectable synchronous and metachronous colorectal liver metastases(CRLM) has not still been defined. The purpose of this study is to compare two treatment strategies in which simultaneous resection of both primary and secondary tumor of synchronous CRLM(SCRLM) and resection of metachronous CRLM(MCRLM) is compared with resection of primary tumor and ablation of secondary tumor in SCRLM and ablation of MCRLM. Endpoints include the rate of severe complications and survival.

Description:

Colorectal cancer(CRC) kills more than 700,000 patients every year, which is nowadays the world's 3rd common and the 4th deadly tumor. About 50% CRC patients will finally develop colorectal liver metastasis (CRLM). Among the CRLM patients, 20-25% of CRC are found with synchronous colorectal liver metastases (SCRLM) at the first visit. Meanwhile, about 20-30% CRC patients suffer by metachronous colorectal liver metastasis (MCRLM) even after radical resection of primary tumor. It is nowadays admitted that the R0 resection of both primary and secondary tumors in SCRLM and R0 resection of MCRLM represents a feasible and potential curative treatment in patients with resectable CRLM(RCRLM). However, the treatment strategy for some RCRLM (tumor number≤3 and tumor size≤3.0cm), such as whether to choose hepatectomy or local ablation, still remains in debate. In primary hepatocellular carcinoma(HCC), local ablation has been proved to has similar curative effect to that of hepatectomy. Compared to hepatectomy, local ablation has less trauma and more rapid recovery and possible lower hospitalization cost. The curative effect of local ablation is mainly influenced by tumor site and tumor size. On the other side, some RCRLM might develop repeat recurrences even after "R0" resection due to the imaging undetectable micro metastasis. Thus, local ablation might be more suitable for some repeat recurrent CRLM. The aim of this study is to compare the efficacy/safety of local ablation with hepatectomy for RCRLM (tumor number≤3, tumor size≤3.0cm), including both SCRLM and MCRLM. Patients are randomized to CRLM resection group and local ablation group. The primary endpoint is overall survival. Secondary endpoints evaluate the rate of patients with at least one severe complication within 30 days after surgery/ablation and long-term clinical outcomes, in particular disease-free survival.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 548
• Est. completion date: July 2026
• Est. primary completion date: July 2021
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. At least one metastatic adenocarcinoma of liver, histologically proven.

2. At least one adenocarcinoma of colon and/or rectum, histologically proven.

3. No local complication at the time of surgery (no occlusion, no sub-occlusion, no massive hemorrhage, no abscesses or local invasion).

4. No extra-hepatic metastasis.

5. Extra-hepatic disease (EHD) suitable for hepatectomy, liver ablation and anesthesia as long as all sites of EHD disease are radically treated.

6. All the primary and secondary tumors which R0 resections are technically possible. (SCRLM: synchronous resection for both primary and secondary tumors, MCRLM: no local recurrence within 6 months after resection of primary tumor)

7. Residual hepatic volume>30%-40%.

8. At least 2-3 hepatic segments remained after hepatectomy (except S1), residual liver with normal portal vein, hepatic artery and biliary duct, at least 1 of hepatic veins (left, middle and right) not invaded.

9. Tumor size =3 cm.

10. Tumor number= 3.

11. Tumors located =1.0 cm of vulnerable structures, e.g. colon, main trunk of portal vein, hepatic artery, hepatic vein and intrahepatic biliary duct.

12. suitable for both hepatectomy and local ablation after multiple disciplinary team(MDT) discussion.

13. Informed written consent.

Exclusion Criteria:

1. Other malignant tumors history.

2. Complications need emergency surgery (occlusion, sub-occlusion, massive hemorrhage and abscesses, et al.).

3. Colorectal or hepatic tumor extension towards abdominal wall and/or adjacent organ making liver R0 resection impossible immediately.

4. Hepatic lesions diagnosed with ultrasound and MRI making complete ablation impossible immediately.

5. = 2 hepatic segments remained after hepatectomy or residual hepatic volume?30%-40%

6. Non resectable lymph node metastasis.

7. American Society of Anesthesiologists(ASA) grading= IV and/or Eastern cooperative oncology group(ECOG) score= 2. (see appendix)

8. EHD is not recommended.

9. Physical or psychological dependence.

10. Pregnant or breast feeding women.

11. Not controlled preoperational infection.

12. Enrolled in other clinical trials within 4 weeks. Other clinical or laboratorial condition not recommended by investigators.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Neoplasms
• Neoplasm Metastasis
• Neoplasms
• Neoplasms, Second Primary
• Secondary Malignant Neoplasm of Liver

Intervention

Procedure:
• CRLM resection group
Simultaneous resection of both primary and secondary tumors in synchronous CRLM or resection of metachronous CRLM.

Device:
• CRLM ablation group
Microwave ablation of CRLM with a 2.15-gigahertz(GHz) microwave generator and a 14 gauge diameter transcutaneous antenna within 30 days after resection of primary tumor in synchronous CRLM or ablation of metachronous CRLM.

Locations

Country	Name	City	State
China	The 6th Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong

Sponsors (3)

Lead Sponsor	Collaborator
Sixth Affiliated Hospital, Sun Yat-sen University	First Affiliated Hospital, Sun Yat-Sen University, Second Affiliated Hospital, Sun Yat-Sen University

Country where clinical trial is conducted

China, 

References & Publications (5)

Bethke A, Kühne K, Platzek I, Stroszczynski C. Neoadjuvant treatment of colorectal liver metastases is associated with altered contrast enhancement on computed tomography. Cancer Imaging. 2011 Jun 29;11:91-9. doi: 10.1102/1470-7330.2011.0015. — View Citation

Brody H. Colorectal cancer. Nature. 2015 May 14;521(7551):S1. doi: 10.1038/521S1a. — View Citation

Joranger P, Nesbakken A, Hoff G, Sorbye H, Oshaug A, Aas E. Modeling and validating the cost and clinical pathway of colorectal cancer. Med Decis Making. 2015 Feb;35(2):255-65. doi: 10.1177/0272989X14544749. Epub 2014 Jul 29. — View Citation

Kopetz S, Chang GJ, Overman MJ, Eng C, Sargent DJ, Larson DW, Grothey A, Vauthey JN, Nagorney DM, McWilliams RR. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol. 2009 Aug 1;27(22):3677-83. doi: 10.1200/JCO.2008.20.5278. Epub 2009 May 26. — View Citation

Livraghi T. Single HCC smaller than 2 cm: surgery or ablation: interventional oncologist's perspective. J Hepatobiliary Pancreat Sci. 2010 Jul;17(4):425-9. doi: 10.1007/s00534-009-0244-x. Epub 2009 Nov 5. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival		3 years	Yes
Secondary	R0 resection rate in both primary and secondary tumor in CRLM		Day of surgery	Yes
Secondary	Death rate during hospitalization or within 30 days after surgery/ablation		30 days after surgery/ablation	Yes
Secondary	Rate of patients with at least one postoperative severe complication within 30 days after surgery/ablation		30 days after surgery/ablation	Yes
Secondary	Disease-free survival and 1, 2 and 3-years disease-free survival rate		1, 2 and 3-years	Yes
Secondary	Complete ablation rate in CRLM		Day of ablation	Yes