DEB-TACE, Lenvatinib and Anti-PD(L)1 Antibody as Conversion Therapy for Intrahepatic Cholangiocarcinoma

NCT06194695 | Unknown

• 1 other identifier: TJ-IRB20221203
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to the efficacy, prognosis, adverse effects, and factors for predicting therapeutic effects and clinical prognosis of combined therapy of Drug-eluting Beads-transarterial chemoembolization (DEB-TACE), lenvatinib, and anti-PD-1/ PD-L1 antibody for patients with advanced intrahepatic cholangiocarcinoma who were initially unsuitable for the radical therapy, including resection, transplantation, or ablation.

Conditions

Cholangiocarcinoma Non-resectable

Keywords

Intrahepatic Cholangiocarcinoma; Lenvatinib; DEB-TACE; anti-PD(L)1 antibodies

Outcome Measures

Primary Outcomes (1)

• Number of Patients Amendable to Curative Surgical Interventions

  Number of patients amendable to curative surgical interventions defined as number of patients receiving curative surgical resection, transplantation, or ablation after successful down-sizing of tumor(s) by intervention.

  from the date of first treatment to the date of last treatment, an average of 3 years

Secondary Outcomes (10)

• overall response rate (ORR) measured by mRECIST criteria

  from the date of first treatment to radiographically documented progression according to mRECIST, assessed up to 3 years]

• Overall survival (OS)

  from the date of first treatment to the date of death from any cause, assessed up to 5 years

• Progression-free survival (PFS)

  from the date of first treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause, whichever occurs first, assessed up to 3 years

• Time to progression (TTP)

  from the date of first treatment to radiographically documented progression according to mRECIST, assessed up to 3 years

• Time to intrahepatic tumor progression (TTITP)

  from the date of first treatment to radiographically documented intrahepatic tumor progression according to mRECIST, assessed up to 3 years

Study Arms (1)

DEB-TACE-len-anti-PD(L)1

Patients with advanced intrahepatic cholangiocarcinoma who was initially evaluated unsuitable for the radical therapy and received combined DEB-TACE plus lenvatinib (Len) and anti-PD1 or anti-PD-L1 antibodies as conversion therapy for downstaging.

Procedure: drug eluting beads-transcatheter arterial chemoembolization; Drug: envatinib plus anti-PD(L)1

Interventions

drug eluting beads-transcatheter arterial chemoembolization PROCEDURE

transcatheter arterial chemoembolization with doxorubicin embedded eluting beads- was performed every 3 weeks through the tumor feeding arteries.

Also known as: DEB-TACE

DEB-TACE-len-anti-PD(L)1

envatinib plus anti-PD(L)1 DRUG

oral use of lenvatinib plus intravenous injection of anti-PD(L)1 antibodies. Anti-PD-L1 antibodies includes duravalumab, atezolizumab, or envolizumab, and anti-PD1 antibodies include pembrolizumab, nivolumab, camrelizumab, tislelizumab, sintilimab, or toripalimab.

DEB-TACE-len-anti-PD(L)1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

patients with unresectable intrahepatic cholangiocarcinoma.

You may qualify if:

• Histologically confirmed intrahepatic cholangiocarcinoma.
• Age ≥18 years.
• ECOG performance status score of 0 or 1.
• Not suitable for radical surgery (including radical hepatic resection, liver transplantation or ablation) after evaluation by the MDT expert group of treating hepatobiliary cancer. Specifically, any of the following conditions are met：
• R0 resection is not feasible.
• in subjects without cirrhosis, the volume of normal liver parenchyma is less than 30% of the total volume, or in patients with cirrhosis, the volume of normal liver parenchyma is less than 40% of the total volume, or ICG-R15\>15%.
• Number of lesions \>1.
• No prior systemic anti-tumor treatment for intrahepatic cholangiocarcinoma before the first dose.
• According to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1), at least 1 measurable lesion, or a measurable lesion that has clearly progressed (based on RECIST V1.1 criteria) after local treatment.
• Subjects with portal vein tumor thrombus (PVTT):
• Chen's group A and B, or Cheng's type I-III can be enrolled.
• Chen's group C, or Cheng's type IV (superior vena cava tumor thrombus) cannot be enrolled.
• Subjects with hepatic vein tumor thrombus:
• VV1 and VV2 types can be enrolled.
• VV3 type, or Sakamoto type I (inferior vena cava tumor thrombus) can also be enrolled.

You may not qualify if:

• Histologically/cytologically confirmed sarcomatoid intrahepatic cholangiocarcinoma, mixed hepatocellular carcinoma, etc.
• History of hepatic encephalopathy or liver transplantation.
• Clinically symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage. Patients with only radiologically detected minimal pleural effusion, ascites, or pericardial effusion without symptoms can be included.
• Acute or chronic active hepatitis B or C infection, with hepatitis B virus (HBV) DNA \>2000IU/ml or 10\^4 copies/ml; hepatitis C virus (HCV) RNA \>10\^3 copies/ml; co-positive for hepatitis B surface antigen (HbsAg) and anti-HCV antibody. Patients who meet the above criteria after antiviral treatment with nucleoside analogs can be included.
• Presence of central nervous system metastases.
• History of esophageal or gastric variceal bleeding due to portal hypertension within the past 6 months. Patients assessed by the investigator to be at high risk of bleeding.
• Any life-threatening bleeding event within the past 3 months, including those requiring blood transfusion, surgery or local treatment, or continuous drug treatment.
• History of arterial or venous thromboembolic events within the past 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other serious thromboembolic events. Exceptions are made for thrombosis formation related to implanted venous infusion ports or catheters, or superficial vein thrombosis that has stabilized after routine anticoagulation treatment. Preventive use of low-dose low molecular weight heparin (such as enoxaparin 40 mg/day) is allowed.
• Continuous use of aspirin (\>325 mg/day) or other known platelet function inhibitors such as clopidogrel or ticlopidine for 10 days within 2 weeks prior to the first dose.
• Uncontrolled hypertension, with systolic blood pressure ≥150mmHg or diastolic blood pressure ≥100mmHg after optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy.
• Presence of any toxicity caused by previous treatment that has not recovered to grade 0 or 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0) before the first dose of study treatment (excluding alopecia, non-clinically significant and asymptomatic laboratory abnormalities).
• Symptomatic congestive heart failure (New York Heart Association class II-IV), left ventricular ejection fraction (LVEF) \<50% as indicated by echocardiography.
• Symptomatic or poorly controlled arrhythmia. History of congenital long QT syndrome or corrected QTc \>500 ms (calculated using the Fridericia formula) at screening.
• Severe bleeding tendency or coagulation disorder, or currently receiving thrombolytic therapy.
• History of gastrointestinal perforation and/or fistula, intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive intestinal resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea within the past 6 months.

Sponsors & Collaborators

• Ze-yang Ding, MD: lead
• Geneplus-Beijing Co. Ltd.: collaborator
• Chinese Cooperative Group of Liver Cancer: collaborator

Study Sites (1)

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

RECRUITING

Related Publications (1)

• Oh DY, Lee KH, Lee DW, Yoon J, Kim TY, Bang JH, Nam AR, Oh KS, Kim JM, Lee Y, Guthrie V, McCoon P, Li W, Wu S, Zhang Q, Rebelatto MC, Kim JW. Gemcitabine and cisplatin plus durvalumab with or without tremelimumab in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, single-centre, phase 2 study. Lancet Gastroenterol Hepatol. 2022 Jun;7(6):522-532. doi: 10.1016/S2468-1253(22)00043-7. Epub 2022 Mar 9.

  PMID: 35278356 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

ctDNA from blood samples, and tumor samples from biopsy of surgical resection will sent for next-generation sequencing.

MeSH Terms

Conditions

Cholangiocarcinoma

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Ze-yang Ding, M.D.

  Tongji Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ze-yang Ding, M.D.

CONTACT

+8613407156200; zyding@tjh.tjmu.edu.cn

Han Gao

CONTACT

+8617730117747; gh1023606887@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: December 22, 2023
• First Posted: January 8, 2024
• Study Start: February 1, 2022
• Primary Completion: December 31, 2024
• Study Completion: June 30, 2025
• Last Updated: January 9, 2024

Record last verified: 2024-01

Locations

CN (1)