Neoadjuvant PDT in the Treatment of Cholangiocarcinoma

A Prospective Randomized Controlled Study of Neoadjuvant PDT in the Treatment of Cholangiocarcinoma

For patients with locally advanced cholangiocarcinoma with resectable margins, patients who meet the selection criteria are randomly divided into two groups A and B. Group A: neoadjuvant PDT therapy combined with radical surgery; Group B: radical surgery. This study aims to explore the clinical effectiveness and safety of neoadjuvant photodynamic therapy for cholangiocarcinoma, as well as its role in destroying local tumors and enhancing systemic inflammation.

Study Overview

• Status: Not yet recruiting
• Conditions: Cholangiocarcinoma Resectable
• Intervention / Treatment: Procedure: Neoadjuvant PDT + radical surgery; Procedure: Radical surgery

Detailed Description

The average 5-year survival rate of patients with cholangiocarcinoma is about 5-10%. Only 30%-40% of patients have the opportunity to obtain radical surgery. Surgical resection is limited by the extent of tumor spread along the bile duct branches and segments, and the degree of involvement of the portal vein and (or) hepatic artery branches. Complete resection with negative margins (R0) is the only possible radical treatment. Only 60%-78% of radical surgery for cholangiocarcinoma are considered to achieve true R0 resection, and the tumor-free margin is often very short. Even after R0 resection, the recurrence rate is as high as 50%-76%. Photodynamic therapy is a tumor specific ablation method with small side effects and repeated treatments will not produce drug resistance. It provides a new prospect for the treatment of cholangiocarcinoma. For the current patients with locally advanced cholangiocarcinoma, neoadjuvant photodynamic therapy is used to make them resectable. Demotion and subsequent resection may potentially improve their results. Similarly, patients with resectable margins can benefit from tumor downgrading by increasing their chances of undergoing R0 resection. In order to increase the negative rate of resection margins, and to ensure sufficient tumor-free margins of the bile duct stumps, the research is still blank. For patients with locally advanced cholangiocarcinoma with resectable margins, patients who meet the selection criteria are randomly divided into two groups A and B. Group A: neoadjuvant PDT therapy combined with radical surgery; Group B: radical surgery. This study aims to explore the clinical effectiveness and safety of neoadjuvant photodynamic therapy, as well as its role in destroying local tumors and enhancing systemic inflammation.This study plans to enroll 50 patients. It is planned to complete the enrollment operation within 2 years, and the follow-up observation will be continued for 5 years after the operation. All patients are expected to complete neoadjuvant PDT treatment and radical surgery within 2 years, survival period (5 years survival rate), R0 resection rate and local recurrence rate are the main observation indicators, and the bilirubin level, the number of intraoperative freezing, the length of the tumor-free margin of the tumor tissue, and the incidence of complications (biliary leakage, cholangitis, phototoxicity) are the secondary observation indicators.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rongfeng Wang, MD; Phone Number: 86-29-85324467; Email: 15877553630@163.com

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • Yi Lv
      • Principal Investigator: Yi Lv, MD,PHD
      • Contact: Xiaogang Zang, MD; Phone Number: 0086-15877553630; Email: 15877553630@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with age between 18 to 75 years;
• Patients'gender was not limited;
• Patients with locally advanced cholangiocarcinoma who have a clear diagnosis of the primary disease and require surgical resection or potential surgical resection;
• No history of radiotherapy and chemotherapy;
• Willing to accept this clinical trial, sign informed consent and be able to cooperate with follow-up.

Exclusion Criteria:

• Women during pregnancy or breastfeeding, and those with mental illness;
• Patients allergic to porphyrin drugs, porphyria;
• Long-term use of glucocorticoids or autoimmune suppression;
• Surgical contraindication, including:

Child-Pugh C with hepatic encephalopathy Anyone with heart, lung, kidney dysfunction or other organ dysfunction, and cannot tolerate surgery.Hepatic ducts stone disease, who was diagnosed as Acute Cholangitis of Severe Type, especially complicated with bacteremia or septic shock. End stage disease, complicated with biliary cirrhosis or portal hypertension.Patients with long- term obstructive jaundice, dehydration, electrolyte disturbance or coagulation defects; Patients have the tendency or history of bleeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: neoadjuvant PDT + radical surgery; Photodynamic therapy for neoadjuvant treatment of cholangiocarcinoma	Procedure: Neoadjuvant PDT + radical surgery; Patients with cholangiocarcinoma will undergo radical surgery after photodynamic therapy
Active Comparator: radical surgery; Patients with cholangiocarcinoma undergo radical surgical resection	Procedure: Radical surgery; Patients with cholangiocarcinoma will only receive radical surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	Compare the incidence of positive margins of bile duct after surgical resection of cholangiocarcinoma between the two groups	During operation
Local recurrence rate	Compare the local recurrence rate of cholangiocarcinoma between the two groups	1-year post operation
Survival time	Compare the 5-year survival time of the two groups	5-year post operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bilirubin level	Compare the Bilirubin level of the two groups	1,3,6,12-month post operation
Complication rate	Compare the incidence of bile leakage, cholangitis, phototoxicity and other complications between the two groups	1, 2,3,4,5,6,7,8-week Post operation
Tumor-free margin length	Compare the length of the tumor-free margin of the two groups of cholangiocarcinoma tissues	During operation

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Xi'an Jiaotong University

Publications and helpful links

General Publications

• Wiedmann M, Caca K, Berr F, Schiefke I, Tannapfel A, Wittekind C, Mossner J, Hauss J, Witzigmann H. Neoadjuvant photodynamic therapy as a new approach to treating hilar cholangiocarcinoma: a phase II pilot study. Cancer. 2003 Jun 1;97(11):2783-90. doi: 10.1002/cncr.11401.
• Wagner A, Wiedmann M, Tannapfel A, Mayr C, Kiesslich T, Wolkersdorfer GW, Berr F, Hauss J, Witzigmann H. Neoadjuvant Down-Sizing of Hilar Cholangiocarcinoma with Photodynamic Therapy--Long-Term Outcome of a Phase II Pilot Study. Int J Mol Sci. 2015 Nov 6;16(11):26619-28. doi: 10.3390/ijms161125978.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2021
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): April 1, 2028

Study Registration Dates

• First Submitted: March 24, 2021
• First Submitted That Met QC Criteria: March 30, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 1, 2021
• Last Update Submitted That Met QC Criteria: March 30, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Cholangiocarcinoma,Neoadjuvant therapy,Photodynamic therapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma
• Other Study ID Numbers: 2020ZDLSF04-08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No