Clinical trial NCT03252808: Phase I Study of TBI-1401(HF10) Plus Chemotherapy in Patients with Unresectable Pancreatic Cancer.
Official title: Phase I Study of Combination with TBI-1401(HF10), a Replication-competent HSV-1 Oncolytic Virus, and Chemotherapy in Patients with Stage III or IV Unresectable Pancreatic Cancer.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Pancreatic Cancer Stage III
Pancreatic Cancer Stage IV
Keywords: Unresectable pancreatic cancer
Metastatic pancreatic cancer
Pancreatic adenocarcinoma
TBI-1401(HF10)
HF10
Oncolytic virus
Oncolytic viral immunotherapy
Gemcitabine
Nab-paclitaxel
Albumin-bound paclitaxel
Abraxane
Tegafur-gimeracil-oteracil potassium
TS-1
canerpaturev
Lead sponsor: Takara Bio Inc.
Sponsor class: INDUSTRY
First posted: 2017-08-17
Enrollment: 36
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the recommended dose of TBI-1401(HF10) treatment in combination with chemotherapy (Gemcitabine + Nab-paclitaxel or TS-1) in patients with stage III or IV unresectable pancreatic cancer.

Detailed description: A Phase I, open-label, multi-center study to determine the recommended dose of TBI-1401(HF10) treatment in combination with chemotherapy (Gemcitabine + Nab-paclitaxel or TS-1) in patients with stage III or IV unresectable pancreatic cancer. Patients with stage IV must failed a gemcitabine based first-line chemotherapy.

Patients with stage III will receive the repeated intratumoral injection of TBI-1401(HF10) at recommended dose at 2-week intervals in combination with intravenous infusion of 1000 mg/m\^2 Gemcitabine and 125 mg/m\^2 Nab-paclitaxel at weekly for 3 weeks followed by 1 week rest.

Patients with stage IV will receive the repeated intratumoral injection of TBI-1401(HF10) at recommended dose at 2-week intervals in combination with oral of 40 - 60 mg TS-1 at twice daily for 4 weeks followed by 2 weeks rest.

Patients will receive the combination therapy of TBI-1401(HF10) + chemo for up to 1 year if eligible for treatment.

Eligibility criteria: Inclusion Criteria:

* Patients with histologically or cytologically confirmed unresectable pancreatic cancer (stage III or IV) based on the General Rules for the Study of Pancreatic Cancer (The 7th edition), and never received anti-cancer therapy (radiation therapy, chemotherapy, immunotherapy, surgery, clinical trials).
* Patients with primary lesion will be intratumorally injectable for TBI-1401(HF10) by EUS (endoscopic ultrasound).
* Patients must be ≧20 years of age.
* Patients must have at least one measurable lesion evaluated by Computed Tomography (CT) scan on RECIST ver.1.1 at pre-treatment.
* Patients must have a life expectancy ≧12 weeks.
* Patients must have an ECOG PS (Eastern Cooperative Oncology Group Performance Status) of 0-1.
* Patients demonstrated adequate organ function (≦7 days prior to treatment).
* Females of childbearing potential must have a negative urine or serum pregnancy test within 1 week prior to start of treatment.
* Patients must be able to understand the study and willing to sign a written informed consent document.

Exclusion Criteria:

* Patients receiving anti-herpes medication within 1 week prior to TBI-1401(HF10) treatment (except local treatment such as ointment).
* Patients with a significant tumor bleeding or coagulation abnormality that could not treat intratumoral injection or biopsy in safe.
* Patients with clinically evident Hepatitis B surface antigen (HBs) positive, Hepatitis C virus (HCV) antibody positive and HSV-RNA positive, Human Immunodeficiency Virus (HIV) antibody positive.
* Patients with the active symptom of Epstein-Barr virus (EBV) infection.
* Patients with active CNS metastases.
* Patients with ascites, except acceptable mild ascites.
* Patients with multiple cancer.
* Patients need to treat anticoagulant or antiplatelet agent.
* Patients has a history of allergy for CT contrast agent, live vaccine, any drug excipients, Nab-paclitaxel, Gemcitabine, or any study drugs.

Primary outcomes:
measure: Dose Limiting Toxicity (DLT)
timeFrame: Through 1st TBI-1401(HF10) injection to before 3rd injection (basically 4 weeks).
Secondary outcomes:
measure: Adverse Events (AEs)
timeFrame: Through 1st TBI-1401(HF10) injection to study completion (up to 13 month).
measure: Objective response rate (ORR) by RECIST
timeFrame: At 16 weeks and through study completion (up to 1 year).
measure: Objective response rate (ORR) by irRECIST
timeFrame: At 16 weeks and through study completion (up to 1 year).
measure: Progression-free survival (PFS) by RECIST
timeFrame: Through disease progression (up to 1 year).
measure: Progression-free survival (PFS) by irRECIST
timeFrame: Through disease progression (up to 1 year).
Other outcomes:
measure: Overall survival (OS)
timeFrame: From 1st treatment to death (up to 2 years).
measure: 1 year survival rate
timeFrame: for 1 year.
Locations:
city: Nagoya
country: Japan
facility: Clinical Site
state: Aichi
city: Kashiwa
country: Japan
facility: Clinical Site
state: Chiba
city: Yokohama
country: Japan
facility: Clinical Site
state: Kanagawa
city: Chūōku
country: Japan
facility: Clinical Site
state: Tokyo
city: Koto-Ku
country: Japan
facility: Clinical Site
state: Tokyo
city: Chiba
country: Japan
facility: Clinical Site
city: Nagoya
country: Japan
facility: Clinical Site
city: Osaka
country: Japan
facility: Clinical Site
Study officials:
affiliation: Clinical Development & Strategy Division 2
name: Takara Bio Inc.
role: STUDY_DIRECTOR
References: