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A Study of Combination With TBI-1401(HF10) and Ipilimumab in Japanese Patients With Unresectable or Metastatic Melanoma

This study is currently recruiting participants.
Verified September 2017 by Takara Bio Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT03153085
First Posted: May 15, 2017
Last Update Posted: September 29, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Takara Bio Inc.
  Purpose
The purpose of this study is to determine if TBI-1401(HF10) in combination with ipilimumab is effective in Japanese patients with stages IIIB, IIIC, or IV unresectable or metastatic melanoma.

Condition Intervention Phase
Melanoma Stage Iii Melanoma Stage Iv Biological: TBI-1401(HF10) Drug: Ipilimumab Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Combination Treatment With TBI-1401(HF10), a Replication-competent HSV-1 Oncolytic Virus, and Ipilimumab in Japanese Patients With Stage IIIB, IIIC, or IV Unresectable or Metastatic Malignant Melanoma

Resource links provided by NLM:


Further study details as provided by Takara Bio Inc.:

Primary Outcome Measures:
  • Best overall response rate (BORR) by irRC [ Time Frame: at 24 weeks ]
    Determine the efficacy of TBI-1401(HF10) in combination with Ipilimumab evaluated by irRC (immuno-related response criteria)


Secondary Outcome Measures:
  • Best overall response rate (BORR) by mWHO response criteria [ Time Frame: at weeks 24 ]
    Determine the efficacy of TBI-1401(HF10) in combination with Ipilimumab evaluated by modified WHO (mWHO) response criteria

  • Objective response rate (ORR) by irRC [ Time Frame: at weeks 6, 12, 18, and 24 ]
    Overall tumor response evaluated by irRC in the measurable target lesion(s) and unmeasurable/evaluable target lesion(s).

  • Objective response rate (ORR) by mWHO [ Time Frame: at weeks 6, 12, 18, and 24 ]
    Overall tumor response evaluated by mWHO response criteria in the measurable target lesion(s) and unmeasurable/evaluable target lesion(s).

  • Adverse event summaries, vital signs, and laboratory parameters to evaluate the safety and tolerability. [ Time Frame: through study completion, up to 1 year ]
    Adverse events will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.0).

  • Progression-free survival (PFS) [ Time Frame: through disease progression, up to 3 years ]
    Evaluation the time to progression during and after the treatment.

  • Durable response rate (DRR) [ Time Frame: for 1 year ]
    Evaluation the length of time after a partial or complete response.

  • 1 year survival rate [ Time Frame: at 1 year ]
    Determine the 1 year survival rate of patient who received treatment.


Other Outcome Measures:
  • Levels of antibody to HSV-1 [ Time Frame: up to weeks 24 ]
    Evaluate the change of anti-HSV-1 antibody levels.

  • Change in immunologic parameters in serum [ Time Frame: up to weeks 24 ]
    Analysis the change of cytokine profiles, antitumor T-cell reactivity and regulatory T-cell (Treg) population by immunoassay and flow cytometry.

  • Histopathological response with TBI-1401(HF10) administrated tumor [ Time Frame: up to weeks 24 ]
    Biopsies will be performed to evaluate the histopathological response with TBI-1401(HF10) administrated tumor.


Estimated Enrollment: 25
Actual Study Start Date: May 25, 2017
Estimated Study Completion Date: December 31, 2018
Estimated Primary Completion Date: June 30, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TBI-1401(HF10) + Ipilimumab
1x10^7 TCID50/mL TBI-1401(HF10) administered to a single or multiple eligible tumors in a total volume up to 5.0 mL (injection volume will be adjusted based on the size of tumor mass) by intratumoral injection and 3 mg/kg ipilimumab administered by intravenous infusions.
Biological: TBI-1401(HF10)

1x10^7 TCID50/mL TBI-1401(HF10) (for a total of 6 injections; the first 4 injections at 1-week intervals; the remaining 2 injections at 3-week intervals).

Following combination therapy, patients may continue to receive the 1x10^7 TCID50/mL TBI-1401(HF10) alone for up to an additional 13 injections (total of 19 injections = 1 year) if eligible for administration.

Other Name: HF10
Drug: Ipilimumab
3 mg/kg ipilimumab (for a total of 4 intravenous infusions, each administered at 3-week intervals).
Other Name: anti CTLA-4 antibody

Detailed Description:

The study is designed to assess efficacy and safety with repeated administration of intratumoral injections of TBI-1401(HF10) at 1x10^7 TCID50/mL in combination with intravenous infusions of 3mg/kg ipilimumab in Japanese patients.

This is a single arm, open label Phase II study, to evaluate the efficacy and safety of TBI-1401(HF10) treatment in combination with the immunologic checkpoint inhibitor, ipilimumab (anti-CTLA-4 monoclonal antibody). The study population will include patients with Stage IIIB, IIIC or IV unresectable or metastatic malignant melanoma who are ipilimumab-eligible.

Patients will receive the dose of 1x10^7 TCID50/mL TBI-1401(HF10) (for a total of 6 injections; the first 4 injections at 1-week intervals; the remaining 2 injections at 3-week intervals) + ipilimumab at 3 mg/kg (for a total of 4 intravenous infusions, each administered at 3-week intervals).

Following combination therapy, patients may continue to receive the 1x10^7 TCID50/mL TBI-1401(HF10) alone for up to an additional 13 injections (total of 19 injections = 1 year) if they have tolerated the study treatment, are responding, have stable disease, or have progressive disease that is not clinically significant in the judgment of the Investigator.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with histologically confirmed Stage IIIB, IIIC or IV unresectable or metastatic melanoma except uveal melanoma, who must have a history of treatment (chemotherapy, molecular targeted therapy, or anti PD-1 antibody therapy).
  • Patients must have measurable non-visceral lesion(s) that are evaluable by the modified World Health Organization (mWHO) criteria and immune-related response criteria (irRC).
  • Patients must be ≥ 20 years of age.
  • Patients must have a life expectancy ≥ 24 weeks.
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • Patients must have adequate organ function, defined as

    • Total bilirubin levels ≤ 1.5 x upper limit of normal [ULN] (except for patients with Gilbert's Syndrome, who must have a total bilirubin of less than 3.0 mg/dL)
    • AST/ALT levels ≤ 2.5 x ULN, or ≤ 5 x ULN if liver metastases are present.
    • Creatinine ≤ 1.5 x ULN or creatinine clearance (calculated) ≥ 60 mL/min/1.73 m^2 for patients with creatinine > 1.5 x ULN.
    • Absolute neutrophil count ≥1,500/µL and
    • Platelet count ≥ 75,000/ µL
  • Men and women of childbearing potential must agree to use adequate contraception from the time of consent through 30 days after final study 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 and willing to sign a written informed consent document.

Exclusion Criteria:

  • Patients who were previously treated with ipilimumab by intravenous infusion.
  • Patients receiving chemotherapy or molecularly targeted drug or anti-PD-1 antibody treatment or radiotherapy or immunotherapy within 4 weeks prior to initiating study treatment.
  • Patients with a history of Grade 4 adverse events caused by chemotherapy, molecularly targeted drug, anti-PD-1 antibody treatment, radiotherapy or immunotherapy conducted more than 4 weeks prior to TBI-1401(HF10) treatment, or presence of such adverse events of Grade 2 or greater, except alopecia and adverse events controlled by a treatment.
  • Patients receiving anti-herpes medication within 1 week prior to initiating TBI-1401(HF10) administration, except local treatment such as ointment.
  • Patients with a history of significant tumor bleeding, or coagulation or bleeding disorders.
  • Patients with target tumors that could potentially invade a major vascular structure (e.g., innominate artery, carotid artery), based on unequivocal imaging findings.
  • Patients with Grade 2 or greater neurologic abnormalities (CTCAE version 4.0), including Grade 2 or greater peripheral neuropathy caused by previous treatments.
  • Patients with clinically evident Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C virus (HCV), or Epstein-Barr virus (EBV) infection.
  • Patients requiring systemic glucocorticoid (except 10 mg/day/body prednisolone or less) or immunosuppressive therapy because of the presence or history of autoimmune disease (e.g., Crohn's disease, ulcerative colitis) or other diseases.
  • Concurrent use of any other investigational agents within 4 weeks prior to initiating study treatment.
  • Patients with active CNS metastases or carcinomatous meningitis, except patients with CNS lesions that have been treated and have no evidence of progression in the brain on CT/MRI for ≥ 3 months.
  • Pregnant or breastfeeding women (excluding the case in which breastfeeding is discontinued and will not resume it); women desiring to become pregnant within the timeframe of the study are also excluded.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, as determined by the investigator.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03153085


Contacts
Contact: Takara Bio Inc +81-77-565-6970 takara-clinical@takara-bio.co.jp

Locations
Japan
Clinical Site Recruiting
Nagakute, Aichi, Japan
Clinical Site Recruiting
Nagoya, Aichi, Japan
Clinical Site Recruiting
Kurume, Fukuoka, Japan
Clinical Site Recruiting
Sapporo, Hokkaido, Japan
Clinical Site Recruiting
Tsukuba, Ibaraki, Japan
Clinical Site Recruiting
Sunto-Gun, Shizuoka, Japan
Clinical Site Recruiting
Chūōku, Tokyo, Japan
Clinical Site Recruiting
Chūō, Yamanashi, Japan
Clinical Site Recruiting
Fukuoka, Japan
Clinical Site Recruiting
Kumamoto, Japan
Clinical Site Recruiting
Niigata, Japan
Clinical Site Recruiting
Ōsaka, Japan
Sponsors and Collaborators
Takara Bio Inc.
Investigators
Principal Investigator: Naoya Yamazaki National Cancer Center Hospital
  More Information

Responsible Party: Takara Bio Inc.
ClinicalTrials.gov Identifier: NCT03153085     History of Changes
Other Study ID Numbers: TBI1401-02
First Submitted: May 8, 2017
First Posted: May 15, 2017
Last Update Posted: September 29, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Takara Bio Inc.:
Unresectable melanoma
Metastatic melanoma
Recurrent Melanoma
TBI-1401(HF10)
HF10
HSV-1
Oncolytic virus
Oncolytic viral immunotherapy
Ipilimumab
Intratumoral administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs