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

NCT ID: NCT05124002

Last Updated: 2024-03-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-01
• Study Completion Date: 2026-04-01

Brief Summary

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.

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.

Conditions

Cholangiocarcinoma, Intrahepatic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Recombinant Human Adenovirus Type 5

Intervention Type: DRUG

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.

HAIC of FOLFOX

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

H101; FOLFOX

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Tsinghua Chang Gung Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ZHANG YUEWEI, MD

Role: PRINCIPAL_INVESTIGATOR

Beijing Tsinghua Chang Gung Hospital

Locations

Beijing Tsinghua Chang Gung Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Wang Tianxiao, MD

Role: CONTACT

wtx419@163.com

0086-13969193950

Facility Contacts

Wang Tianxiao, MD

Role: primary

wtx419@163.com

+86 13969193950

Other Identifiers

21325-2-02

Identifier Type: -

Identifier Source: org_study_id