Phase I Study of TBI-1401(HF10) Plus Chemotherapy in Patients with Unresectable Pancreatic Cancer.

Takara Bio

Status and phase: Active, not recruiting; Phase 1

Conditions: Pancreatic Cancer Stage III; Pancreatic Cancer Stage IV

Treatments: Biological: TBI-1401(HF10); Drug: Gemcitabine; Drug: TS-1; Drug: Nab-paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT03252808

TBI1401-03

Details and patient eligibility

About

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.

Full 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.

Enrollment: 36 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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36 participants in 3 patient groups

TBI-1401(HF10) + Gem/nab-PTX

Experimental group

Description:

1x10\^6 or 1x10\^7 TCID50/mL TBI-1401(HF10) administered to the tumor in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection and 1000 mg/m\^2 Gemcitabine and 125 mg/m\^2 Nab-paclitaxel injected by intravenous infusions.

Treatment:

Drug: Nab-paclitaxel

Drug: Gemcitabine

Biological: TBI-1401(HF10)

TBI-1401(HF10) + TS-1 (primary)

Experimental group

Description:

1x10\^6 or 1x10\^7 TCID50/mL TBI-1401(HF10) administered to the primary tumor in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection and TS-1 administered by oral.

Treatment:

Drug: TS-1

Biological: TBI-1401(HF10)

TBI-1401(HF10) + TS-1 (primary and meta)

Experimental group

Description:

1x10\^6 or 1x10\^7 TCID50/mL TBI-1401(HF10) administered to the primary tumor in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection and hepatic metastasis in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection or percutaneous injection and TS-1 administered by oral.

Treatment:

Drug: TS-1

Biological: TBI-1401(HF10)