Divestment for Artery-involved Pancreatic Cancer

Pancreatic Cancer Clinical Trial

Official title:

Artery Divestment Technique in Artery-Involved Pancreatic Cancer: A Single-Institution, Open-Labeled Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03443921
• Other study ID #: NMU-JSPH-PC-DIV
• Status: Not yet recruiting
• Phase: N/A
• First received: December 17, 2017
• Last updated: February 18, 2018
• Start date: March 2018
• Est. completion date: March 2021

Study information

• Verified date: February 2018
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: Yi Miao, MD, PhD
• Phone: +86-25-68136508
• Email: miaoyi[@]njmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Pancreatic cancer is the most lethal malignancy of human being. Surgery is the only potential cure of pancreatic cancer. The invasion of major abdominal arteries is one of the most important factor restricting surgical intervention. For artery-involved pancreatic cancer (ai-PC) patients, pre-operative adjuvant therapies, especially the neoadjuvant chemotherapy, has brought exciting postoperative survival. Yet due to the potential screening effect of this treatment strategy, nearly half of ai-PC patients failed to benefit from surgery because of disease progression, adverse reactions of adjuvant treatment and other reasons. Artery divestment for the treatment of ai-PC firstly reported by our center, can significantly increase resection rate and produce overall survival benefit in some patients. This study is to explore whether up-front surgery with artery divestment combined curative pancreatectomy or the chemotherapy-first strategy would be more beneficial for ai-PC patients' survival.

Subjects will be randomized to treatment group either receiving up-front artery divestment combined pancreatectomy (Surgery Group) or adjuvant chemotherapies (Chemo Group). In Surgery Group, an artery divestment combined pancreatectomy will be performed if no pre-operative contra-indication or intra-operative metastasis were revealed. Post-operative adjuvant chemotherapies were prescribed according to performance status. In Chemo Group, adjuvant chemotherapy of gemcitabine or gemcitabine + cisplatin will be utilized according to performance status. After 2 circles of adjuvant chemotherapies, patients will be reevaluated and curative operation would be attempted if without disease progression.

Overall mortality at one year after randomization will be the primary endpoint. Other parameters as overall survival after 2 and 3 years, median survival, disease-free survival, margin status of subjects receiving curative surgery, etc. will also be observed.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 122
• Est. completion date: March 2021
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Diagnosed with pancreatic cancer staged at cT4NxM0(AJCC Cancer Staging Manual, 8th Edition) based on contrast enhanced CT&MRI scan and tumor markers;

2. Age > 18 year and <80 year;

3. Agree to participate in the study with signed informed consent.

Exclusion Criteria:

1. Evidence of metastasis based on physical examination, enhanced CT or enhanced MRI;

2. Poor performance status and/or co-morbidity precluding pancreatectomy and chemotherapy;

3. Focal vessel narrowing or contour irregularity revealed by radiology examinations;

4. Economic situations cannot afford designed treatment.

Related Conditions & MeSH terms

• Borderline Resectable Pancreatic Cancer
• Locally Advanced Pancreatic Cancer
• Neoadjuvant Therapy
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Procedure:
• Artery Divestment Technique
Tunica adventitia was pick up by forceps and opened by electrocoagulation at 1 cm distal from tumor-artery contact. Space between tunica adventitia and external elastic lamina (EEL) were blunt lifting tumor-invaded adventitia by angled clamp. Adventitia was then sectioned to show EEL. Loose dissect space could be achieve along long the plane between EEL and adventitia as long as tumor invasion outside EEL. Tumor and invaded adventitia were further cut open by electrocoagulation proximally. Circumferentially, separation could be done by blunt dissection around EEL. Nourishing blood vessels of the artery would be secured by electrocoagulation or ultrasonic scalpel while major branch would be ligated or transfixed.

Drug:
• Nab-paclitaxel
After eligibility testing as blood tests, contrast-enhanced CT and MRI scan, 3 cycles were administered (1,000 mg/m2 of gemcitabine and 125 mg/m2 of nab-paclitaxel on days 1, 8, and 15 every 28 days).Patients will be reevaluated and curative operation would be attempted if without disease progression.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital with Nanjing Medical University

Country where clinical trial is conducted

China, 

References & Publications (7)

Chua TC, Saxena A. Extended pancreaticoduodenectomy with vascular resection for pancreatic cancer: a systematic review. J Gastrointest Surg. 2010 Sep;14(9):1442-52. doi: 10.1007/s11605-009-1129-7. Epub 2010 Apr 9. Review. — View Citation

Fortner JG, Kim DK, Cubilla A, Turnbull A, Pahnke LD, Shils ME. Regional pancreatectomy: en bloc pancreatic, portal vein and lymph node resection. Ann Surg. 1977 Jul;186(1):42-50. — View Citation

Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med. 2014 Nov 27;371(22):2140-1. doi: 10.1056/NEJMc1412266. — View Citation

Seufferlein T, Bachet JB, Van Cutsem E, Rougier P; ESMO Guidelines Working Group. Pancreatic adenocarcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012 Oct;23 Suppl 7:vii33-40. — View Citation

Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7-30. doi: 10.3322/caac.21387. Epub 2017 Jan 5. — View Citation

Tang K, Lu W, Qin W, Wu Y. Neoadjuvant therapy for patients with borderline resectable pancreatic cancer: A systematic review and meta-analysis of response and resection percentages. Pancreatology. 2016 Jan-Feb;16(1):28-37. doi: 10.1016/j.pan.2015.11.007. Epub 2015 Dec 2. Review. — View Citation

Zhang H, Wroblewski K, Jiang Y, Penney BC, Appelbaum D, Simon CA, Salgia R, Pu Y. A new PET/CT volumetric prognostic index for non-small cell lung cancer. Lung Cancer. 2015 Jul;89(1):43-9. doi: 10.1016/j.lungcan.2015.03.023. Epub 2015 Apr 9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall mortality at one year after randomization;		1 year
Secondary	Overall survival rate after 2 years from randomization;		2 years
Secondary	Overall survival rate after 3 years from randomization;		3 years
Secondary	Median survival		3 years
Secondary	Disease-free survival		3 years
Secondary	Margin status of subjects receiving curative surgery	The margin status will be reported as R0, R1 and R2 according to AJCC Cancer Staging Manual 8th ed.	1 years
Secondary	Intra-operative blood transfusion	For both Surgery Group and participants who received operations in NeoChemo Group, category and volume of intra-operative blood transfusion will be reported.	1 years
Secondary	Intra-operative blood loss	For both Surgery Group and participants who received operations in NeoChemo Group, intra-operative blood loss will be measured and reported by milliliter.	1 years
Secondary	Overall surgical complication rate	Overall surgical complication rate for both Surgery Group and participants who received operations in NeoChemo Group will be reported. Post-operative pancreatic fistula, delayed gastric emptying, post-operative hemorrhage, Surgical site infection and other surgical complications will be recorded. Percentage that candidates suffered from surgical complications of surgical cases for both group will be reported.	1 years
Secondary	Incidence of post-operative pancreatic fistula	Post-operative pancreatic fistula (POPF) will be accessed byInternational Study Group of Pancreatic Surgery (ISGPS) standards; Incidence of post-operative pancreatic fistula of surgical cases in both group will be reported.	1 years
Secondary	Incidence of delayed gastric emptying	Delayed gastric emptying (DGE) will be accessed byInternational Study Group of Pancreatic Surgery (ISGPS) standards; Incidence of DGE of surgical cases in both group will be reported.	1 years
Secondary	Incidence of post-operative hemorrhage	Post-operative hemorrhage (POH) will be accessed byInternational Study Group of Pancreatic Surgery (ISGPS) standards; Incidence of POH of surgical cases in both group will be reported.	1 years
Secondary	Incidence of surgical site infection	Surgical site infection was assessed as US CDC guidelines.Incidence of surgical site infection of surgical cases in both group will be reported.	1 years
Secondary	Incidence of other surgical complications	Any other undesirable situations that considered complicated with surgery will be recorded. Incidence of other surgical complications of surgical cases in both group will be reported.	1 years
Secondary	Severe adverse events rate	Feasibility of chemotherapy will be evaluated according to Common Terminology Criteria for Adverse Events, US NCI. Participants receiving neo-adjuvant, adjuvant or palliative chemotherapy will be accessed. Grade 3-5 adverse events, dose reduction or dose delay will be reported.	3 years
Secondary	Quality of life at 0.5 year after randomization	EORTC QLQ-C30 (V3.0) will be enrolled to evaluate quality of life.	0.5 year
Secondary	Quality of life at 1 year after randomization	EORTC QLQ-C30 (V3.0) will be enrolled to evaluate quality of life.	1 year
Secondary	Quality of life at 2 years after randomization	EORTC QLQ-C30 (V3.0) will be enrolled to evaluate quality of life.	2 years
Secondary	Quality of life at 3 years after randomization	EORTC QLQ-C30 (V3.0) will be enrolled to evaluate quality of life.	3 years
Secondary	Performance status at 0.5 year after randomization	Karnofsky Performance Status Scale will be enrolled to evaluate Performance status.	0.5 year
Secondary	Performance status at 1 year after randomization	Karnofsky Performance Status Scale will be enrolled to evaluate Performance status.	1 year
Secondary	Performance status at 2 years after randomization	Karnofsky Performance Status Scale will be enrolled to evaluate Performance status.	2 years
Secondary	Performance status at 3 years after randomization	Karnofsky Performance Status Scale will be enrolled to evaluate Performance status.	3 years