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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Cholangiocarcinoma, Intrahepatic

Intervention / Treatment
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* Drug: Recombinant Human Adenovirus Type 5
* Drug: HAIC of FOLFOX


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: HAIC (FOLFOX) + H101
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: H101+HAIC<br>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<br>* 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.<br>* Other names: H101;Drug: HAIC of FOLFOX<br>* 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.<br>* Other names: FOLFOX;|

What is the study measuring?
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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 year | 

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 1 year | 
| 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 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oncolytic virus, intrahepatic mass-forming cholangiocarcinoma