Cholangiocarcinoma, Intrahepatic
Conditions
Keywords
oncolytic virus, intrahepatic mass-forming cholangiocarcinoma
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.
Interventions
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.
DRUGHAIC 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.
Sponsors
Beijing Tsinghua Chang Gung Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
HAIC (FOLFOX) + H101
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | up to 1 month | The median amount of time from registration until disease progression or death, whichever occurs first. Disease progression was assessed via RECIST 1.1 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1 year survival rate | 1 year | The percentage of participants who are alive one year after the start of the treatment. |
| Objective response rate (ORR) | up to 1month | The percentage of participants who have achieved either a complete or partial response, as assessed by Response Criteria in Solid Tumors (RECIST 1.1). |
| Disease control rate (DCR) | up to 1 month | 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). |
Countries
China
Contacts
Primary ContactWang Tianxiao, MD
Outcome results
None listed