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

Phase 1

Active, not recruiting

• Conditions: Pancreatic Cancer Stage III; Pancreatic Cancer Stage IV
• Interventions: Biological: TBI-1401(HF10); Drug: TS-1; Drug: Gemcitabine; Drug: Nab-paclitaxel

• Registration Number: NCT03252808
• Lead Sponsor: Takara Bio Inc.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-08-09
• Study First Submitted QC: 2017-08-16
• Study First Posted: 2017-08-17
• Study Start: 2017-09-25
• Primary Completion: 2020-02-19
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-04
• Last Update Posted: 2024-12-09
• Study Completion: 2035-03-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 36

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TBI-1401(HF10) + Gem/nab-PTX	Nab-paclitaxel	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.
TBI-1401(HF10) + Gem/nab-PTX	TBI-1401(HF10)	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.
TBI-1401(HF10) + TS-1 (primary)	TBI-1401(HF10)	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.
TBI-1401(HF10) + TS-1 (primary)	TS-1	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.
TBI-1401(HF10) + TS-1 (primary and meta)	TBI-1401(HF10)	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.
TBI-1401(HF10) + TS-1 (primary and meta)	TS-1	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.
TBI-1401(HF10) + Gem/nab-PTX	Gemcitabine	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.

Primary Outcome Measures

Name	Time	Method
Dose Limiting Toxicity (DLT)	Through 1st TBI-1401(HF10) injection to before 3rd injection (basically 4 weeks).	Determine the recommended dose of TBI-1401(HF10) in combination with Gemcitabine and Nab-paclitaxel.

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR) by irRECIST	At 16 weeks and through study completion (up to 1 year).	Overall tumor response evaluated by irRECIST.
Adverse Events (AEs)	Through 1st TBI-1401(HF10) injection to study completion (up to 13 month).	Evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.0).
Progression-free survival (PFS) by irRECIST	Through disease progression (up to 1 year).	Evaluation the time to progression during and after the treatment.
Objective response rate (ORR) by RECIST	At 16 weeks and through study completion (up to 1 year).	Overall tumor response evaluated by RECIST version 1.1
Progression-free survival (PFS) by RECIST	Through disease progression (up to 1 year).	Evaluation the time to progression during and after the treatment.

Trial Locations

Locations (1)

Clinical Site; 🇯🇵 Osaka, Japan