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.

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.

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