Clinical trial NCT04824742: Neoadjuvant PDT in the Treatment of Cholangiocarcinoma
Official title: A Prospective Randomized Controlled Study of Neoadjuvant PDT in the Treatment of Cholangiocarcinoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Cholangiocarcinoma Resectable
Keywords: Cholangiocarcinoma,Neoadjuvant therapy,Photodynamic therapy
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
First posted: 2021-04-01
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: R0 resection rate
timeFrame: During operation
measure: Local recurrence rate
timeFrame: 1-year post operation
measure: Survival time
timeFrame: 5-year post operation
Secondary outcomes:
measure: Bilirubin level
timeFrame: 1,3,6,12-month post operation
measure: Complication rate
timeFrame: 1, 2,3,4,5,6,7,8-week Post operation
measure: Tumor-free margin length
timeFrame: During operation
Other outcomes:
Locations:
city: Xi'an
country: China
facility: Yi Lv
state: Shaanxi
Study officials:
affiliation: China, Shaanxi First Affiliated Hospital of Xian JiaotongUniversity
name: Yi Lv, MD,PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.