recombinant human adenovirus type 5 plus haic of folfox for intrahepatic cholangiocarcinoma

Conditions: Cholangiocarcinoma, Intrahepatic

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.

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.

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

Keywords: oncolytic virus intrahepatic mass-forming cholangiocarcinoma