A Study of TBI-1401(HF10) in Patients With Solid Tumors With Superficial Lesions

A Phase I Study of Repeated Intratumoral Administration of TBI-1401(HF10), a Replication Competent HSV-1 Oncolytic Virus, in Patients With Solid Tumors With Superficial Lesions

The purpose of this study is to determine whether TBI-1401(HF10), a spontaneously attenuated mutant of Herpes Simplex Virus Type 1 (HSV-1), is safe and tolerable in the treatment of solid tumors with superficial lesions.

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Biological: TBI-1401(HF10); Biological: TBI-1401(HF10)

Detailed Description

This is an open label, non-randomized, dose escalation Phase I study evaluating the repeated intratumoral administrations of the TBI-1401(HF10), a spontaneously attenuated mutant of HSV-1, in patients with solid tumors with superficial lesions (e.g., malignant melanoma and squamous cell carcinoma of the skin).

The study will evaluate the safety and tolerability of repeated intratumoral administrations of TBI-1401(HF10) at dose levels of 1 x 10^6 TCID50/dose (cohort 1) and 1 x 10^7 TCID50/dose (cohort 2) in Japanese patients. Three patients will be enrolled in each cohort. Patients in the each cohort will receive a total of four intratumoral administrations in the same lesion.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologically confirmed solid tumors with superficial lesions.
• Patients must have unresectable and standard therapies-resistant solid tumors.
• Patients must be ≥ 20 years of age.
• Patients must have a life expectancy ≥ 12 weeks.
• Patients must have measurable non-visceral lesion(s) that are evaluable by the mWHO response criteria.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

• Patients must have adequate key organ function (bone marrow, heart, lung, liver, renal, etc), as defined as

  • Absolute neutrophil count ≥ 1,500/μL.
  • Platelet count ≥ 100,000/μL.
  • Total bilirubin levels ≤ 1.5 x upper limit of normal (ULN).
  • AST/ALT levels ≤ 2.5 x ULN, or ≤ 5 x ULN if liver metastases are present.
  • creatinine ≤ 1.5 x ULN.
  • creatinine clearance (calculated) ≥ 60 mL/min/1.73 m^2 for patients with creatinine > 1.5 x ULN.
• Patients must have passed 4 weeks after the completion of prior therapy [except bone metastasis therapy], or passed 8 weeks if immuno checkpoint inhibitor was treated.
• Patients must be able to understand and willing to sign a written informed consent document.

Exclusion Criteria:

• Patients with a history of significant tumor bleeding, or coagulation or bleeding disorders.
• Patients with Grade 2 adverse events Grade 2 or greater, except alopecia, resulting from anticancer agents administered more than 4 weeks prior to TBI-1401(HF10) administration.
• Patients receiving anti-herpes medication [except local treatment such as ointment].
• Patients receiving steroids or immunosuppressive agents [except inhaled steroid].
• Patients with clinically evident Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C virus (HCV) infection.
• Patients receiving anti-platelet medication.
• Patients receiving anti-coagulation medication.
• Patients with presence or medical history of central nervous system metastasis.
• Patients with Grade ≥ 2 pre-existing neurologic abnormalities (CTCAE version 4.0).
• Patients with severe cardiac disorder or abnormal cardiac rhythm.
• Patients with psychiatric disorder or drug dependency which affects informed consent.
• Pregnant or breastfeeding women; women or men, having normal reproductive potential, who disagree with the protection of pregnancy within the timeframe of the study.
• Patients received any other investigational products within 4 weeks, or within 8 weeks if immuno checkpoint inhibitor was treated.
• Patients would limit compliance with study requirements, as determined by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TBI-1401(HF10) - Cohort 1; Oncolytic virotherapy, intratumoral administrations of TBI-1401(HF10)	Biological: TBI-1401(HF10); Patients will receive intratumoral administrations of TBI-1401(HF10). The dose is 1 mL of 1x10^6 TCID50/mL.; Biological: TBI-1401(HF10); Patients will receive intratumoral administrations of TBI-1401(HF10). The dose is 1 mL of 1x10^7 TCID50/mL.
Experimental: TBI-1401(HF10) - Cohort 2; Oncolytic virotherapy, intratumoral administrations of TBI-1401(HF10)	Biological: TBI-1401(HF10); Patients will receive intratumoral administrations of TBI-1401(HF10). The dose is 1 mL of 1x10^6 TCID50/mL.; Biological: TBI-1401(HF10); Patients will receive intratumoral administrations of TBI-1401(HF10). The dose is 1 mL of 1x10^7 TCID50/mL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability (CTCAE version 4.0).	Adverse events will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.0).	up to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall tumor response (modified World Health Organization response criteria)	Overall tumor response will be evaluated by modified World Health Organization (mWHO) response criteria in the measurable target lesion(s) and unmeasurable/evaluable target lesion(s).	at Week 12
Levels of antibody to HSV-1	Anti-HSV-1 antibodies will be assessed in serum.	up to Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cytokine profiles in serum	Evaluation of cytokine profiles in serum by immunoassay.	up to Week 12
Change in antitumor T-cell reactivity in serum	Antitumor T-cell reactivity in serum will be evaluated by flow cytometry.	up to Week 12
Change in regulatory T-cell (Treg) population in serum	Treg population in serum will be evaluated by flow cytometry.	up to Week 12
Histopathological response with TBI-1401(HF10) administrated tumor	Core biopsies will be performed to evaluate the histopathological response with TBI-1401(HF10) administrated tumor.	at Week 12

Collaborators and Investigators

• Sponsor: Takara Bio Inc.
• Investigators: Principal Investigator: Naoya Yamazaki, National Cancer Center Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: April 16, 2015
• First Submitted That Met QC Criteria: April 22, 2015
• First Posted (Estimate): April 28, 2015

Study Record Updates

• Last Update Posted (Actual): July 2, 2017
• Last Update Submitted That Met QC Criteria: June 29, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Phase I; Melanoma; TBI-1401(HF10); HF10; Oncolytic virus; HSV-1; Intratumoral administration; Oncolytic virotherapy
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: TBI1401-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided