Combined HAIC, Lenvatinib and Pucotenlimab As Conversion Therapy for Unresectable Intrahepatic Cholangiocarcinoma

NCT06192797 | Recruiting Phase 2 DMC

• 1 other identifier: 2023-S080
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-arm, phase 2 study. The purpose of study is to evaluate the feasibility and safety of hepatic artery infusion chemotherapy combined with lenvatinib and pucotenlimab as conversion therapy for unresectable intrahepatic cholangiocarcinoma.

Conditions

Cholangiocarcinoma Non-resectable

Keywords

Intrahepatic Cholangiocarcinoma; Pucotenlimab; Lenvatinib; HAIC

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)

HAIC-len-puco

EXPERIMENTAL

Patients with advanced intrahepatic cholangiocarcinoma who was initially evaluated unsuitable for the radical therapy and received combined HAIC plus lenvatinib (Len) and pucotenlimab as conversion therapy for downstaging.

Procedure: HAIC; Drug: Lenvatinib plus pucotenlimab

Interventions

HAIC PROCEDURE

administration of gemcitabine and oxaliplatin via the tumor feeding arteries every 3 weeks.

Also known as: hepatic arterial infusion chemotherapy of GEMOX

HAIC-len-puco

Lenvatinib plus pucotenlimab DRUG

lenvatinib (8mg, qd) plus pucotenlimab (200mg, q3w)

Also known as: levima plus pucotenlimab

HAIC-len-puco

Eligibility Criteria

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

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

• Tongji Hospital: lead

Study Sites (1)

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

Wuhan, Hubei, 430030, China

RECRUITING

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Ze-yang Ding

  Tongji Hospital

  STUDY CHAIR

Central Study Contacts

Ze-yang Ding

CONTACT

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

Han Gao

CONTACT

+8617730117747; gh1023606887@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: December 9, 2023
• First Posted: January 5, 2024
• Study Start: June 11, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2028
• Last Updated: November 5, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)