Recombinant Human Adenovirus Type 5 Plus HAIC of FOLFOX for Intrahepatic Cholangiocarcinoma

Recombinant Human Adenovirus Type 5 Combined With Hepatic Artery Infusion Chemotherapy of FOLFOX in Patients With Intrahepatic Mass-forming Cholangiocarcinoma: a Single-site, Single-arm, Prospective Study

Oncolytic viruses can selectively replicate in and destroy tumor cells. Recent studies indicate that recombinant human adenovirus type 5 (H101), which is the first approved oncolytic virus drug in the world, shows anti-tumor effects on liver cancer. This study aims to further verify the effect and safety of recombinant human adenovirus type 5 combined with HAIC in the treatment of intrahepatic mass-forming cholangiocarcinoma.

Study Overview

• Status: Recruiting
• Conditions: Cholangiocarcinoma, Intrahepatic
• Intervention / Treatment: Drug: Recombinant Human Adenovirus Type 5; Drug: HAIC of FOLFOX

Detailed Description

This is a perspective, single-arm trial. According to previous studies, the PFS of HAIC for unresectable intrahepatic cholangiocarcinoma is approximately 8 - 10 months, and one year progression free rate is about 40%. We assumed that the study could detect 20% absolute difference and 1 year PFS rate could achieve 60% PFS by (FOLFOX + H101) over conventional HAIC (FOLFOX). Simon's two-stage design is used to estimate the sample size, with α value of 0.05 and power of 0.9. A total sample size of 66 participants are required.

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Wang Tianxiao, MD; Phone Number: 0086-13969193950; Email: wtx419@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 102218
      • Recruiting
      • Beijing Tsinghua Chang Gung Hospital
      • Contact: Wang Tianxiao, MD; Phone Number: +86 13969193950; Email: wtx419@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years, male or female
• Histologically or cytologically confirmed intrahepatic mass-forming cholangiocarcinoma (IMCC) with unresectable lesion(s) or patients who refuse surgery
• At least one measurable lesion according RECIST v1.1 criteria [spiral CT/MRI scan ≥ 10 mm (CT scan slice thickness no greater than 5 mm)]
• Life expectancy ≥ 3 months
• The function of vital organs meets the following requirements: absolute neutrophil count (ANC) ≥ 3.5 × 10^9/L; platelets ≥ 125 × 10^9/L; hemoglobin ≥ 8 g/dL; Serum albumin ≥ 2.8 g/dL; bilirubin ≤ 3 ULN, ALT/AST ≤ 2.5 ULN; ALT/AST in the presence of liver metastases ≤ 5 ULN; creatinine ≤ 1.5 ULN; euthyroid; LVEF > 50%
• The date of the first dose of study drug is ≥ 21 days from the date of previous anti-tumor treatment, and has recovered from adverse reactions to prior anti-tumor therapy to baseline or lower than grade 1 (according to CTCAE Version 5.0)(except alopecia)
• Female patients of childbearing potential (including early menopause, menopause < 2 years, and non-surgical sterilization), male patients and their partners must agree to use effective contraceptive measures during the study
• Patients or their legal representatives can understand and offer informed consent, being willing to take part in the follow-up with good compliance

Exclusion Criteria:

• Pregnant or lactating women, men or women who are reluctant to take effective contraceptive measures
• Previous treatment with oncolytic viruses (such as T-VEC)
• Abnormal coagulation function, or having a bleeding tendency, or receiving thrombolytic or anticoagulant therapy
• Patients with poor glycemic control
• Known central nervous system tumors, including metastatic brain tumors
• Accompanied by any unstable systemic diseases, including but not limited to severe infection, resistant hypertension, unstable angina, stroke or myocardial infarction within 6 months, congestive heart failure, and serious cardiac arrhythmia requiring medication, renal or metabolic disease requiring medication
• Known hypersensitivity to the study drug or oxaliplatin, leucovorin calcium, fluorouracil
• History of immunodeficiency or autoimmune disease, or receiving long-term systemic steroid therapy within 7 days before enrollment, or any form of immunosuppressive therapy
• Other conditions that are not suitable for participating in this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: H101+HAIC; Recombinant Human Adenovirus Type 5 (H101): intratumorally injected 3 days before HAIC. 1 vial (5.0 × 10^11 vp) if the maximum diameters of lesion ≤ 5 cm, 2 vials (1.0 × 10^12 vp) if the maximum diameters of lesion ≤ 10 cm, 3 vials (1.5 × 10^12 vp) if the maximum diameters of lesion is > 10 cm. HAIC (FOLFOX): Oxaliplatin 50 mg + 5-FU 1.5 g + leucovorin calcium

Drug: Recombinant Human Adenovirus Type 5; H101 will be intratumorally injected 3 days before HAIC. Dosage of H101: 1 vial (5.0 × 10^11 vp) if the maximum diameters of lesion ≤ 5 cm, 2 vials (1.0 × 10^12 vp) if the maximum diameters of lesion ≤ 10 cm, 3 vials (1.5 × 10^12 vp) if the maximum diameters of lesion is > 10 cm.; Other Names: H101; Drug: HAIC of FOLFOX; Oxaliplatin 50 mg + 5-FU 1.5 g + leucovorin calcium. The infusion will be continued for 2-3 days according to patients' tolerance and tumor conditions. The standard treatment for HAIC consists of 4-6 cycles, with the second cycle being 3 weeks after the end of the first HAIC cycle and the subsequent cycles being 4 weeks after the end of the previous HAIC.; Other Names: FOLFOX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	The median amount of time from registration until disease progression or death, whichever occurs first. Disease progression was assessed via RECIST 1.1 criteria.	up to 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1 year survival rate	The percentage of participants who are alive one year after the start of the treatment.	1 year
Objective response rate (ORR)	The percentage of participants who have achieved either a complete or partial response, as assessed by Response Criteria in Solid Tumors (RECIST 1.1).	up to 1month
Disease control rate (DCR)	The percentage of participants who have achieved complete response, partial response and stable disease, as assessed by Response Criteria in Solid Tumors (RECIST 1.1).	up to 1 month

Collaborators and Investigators

• Sponsor: Beijing Tsinghua Chang Gung Hospital
• Investigators: Principal Investigator: ZHANG YUEWEI, MD, Beijing Tsinghua Chang Gung Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: October 31, 2021
• First Submitted That Met QC Criteria: November 15, 2021
• First Posted (Actual): November 17, 2021

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: oncolytic virus; intrahepatic mass-forming cholangiocarcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma
• Other Study ID Numbers: 21325-2-02

Drug and device information, study documents

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