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

Pancreatic Cancer Stage IV Clinical Trial

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03252808
• Other study ID #: TBI1401-03
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 25, 2017
• Est. completion date: March 31, 2035

Study information

• Verified date: November 2023
• Source: Takara Bio Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. completion date: March 31, 2035
• Est. primary completion date: February 19, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pancreatic Cancer Stage III
• Pancreatic Cancer Stage IV
• Pancreatic Neoplasms

Intervention

Biological:
• TBI-1401(HF10)
1x10^6 or 1x10^7 TCID50/mL TBI-1401(HF10) administered by intratumoral injection at 2-week intervals. Patients may continue to receive the injections for up to 1 year if eligible for injection.

Drug:
• Gemcitabine
1000 mg/m^2 Gemcitabine administered by intravenous infusion at weekly for 3 weeks followed by a week of rest.
• Nab-paclitaxel
125 mg/m^2 Nab-paclitaxel administered by intravenous infusion at weekly for 3 weeks followed by a week of rest.
• TS-1
TS-1 (40-60 mg per body surface area) administered by oral at twice daily for 4 weeks followed by 2 weeks of rest.

Locations

Country	Name	City	State
Japan	Clinical Site	Chiba
Japan	Clinical Site	Chuoku	Tokyo
Japan	Clinical Site	Kashiwa	Chiba
Japan	Clinical Site	Koto-Ku	Tokyo
Japan	Clinical Site	Nagoya
Japan	Clinical Site	Nagoya	Aichi
Japan	Clinical Site	Osaka
Japan	Clinical Site	Yokohama	Kanagawa

Sponsors (1)

Lead Sponsor	Collaborator
Takara Bio Inc.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall survival (OS)	Evaluation the overall survival.	From 1st treatment to death (up to 2 years).
Other	1 year survival rate	Determine the 1 year survival rate of patient who received treatment.	for 1 year.
Primary	Dose Limiting Toxicity (DLT)	Determine the recommended dose of TBI-1401(HF10) in combination with Gemcitabine and Nab-paclitaxel.	Through 1st TBI-1401(HF10) injection to before 3rd injection (basically 4 weeks).
Secondary	Adverse Events (AEs)	Evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.0).	Through 1st TBI-1401(HF10) injection to study completion (up to 13 month).
Secondary	Objective response rate (ORR) by RECIST	Overall tumor response evaluated by RECIST version 1.1	At 16 weeks and through study completion (up to 1 year).
Secondary	Objective response rate (ORR) by irRECIST	Overall tumor response evaluated by irRECIST.	At 16 weeks and through study completion (up to 1 year).
Secondary	Progression-free survival (PFS) by RECIST	Evaluation the time to progression during and after the treatment.	Through disease progression (up to 1 year).
Secondary	Progression-free survival (PFS) by irRECIST	Evaluation the time to progression during and after the treatment.	Through disease progression (up to 1 year).