Clinical Trials /

NT-I7 for the Treatment of Recurrent Squamous Cell Carcinoma of Head and Neck Undergoing Surgery

NCT04588038

Description:

This phase I trial evaluates the side effects of NT-I7 in treating patients with squamous cell carcinoma of head and neck that has come back (recurrent) who are undergoing surgery. NT-I7 is an immunotherapy drug that works by helping the immune system fight tumor cells. The body produces T-cells which play an important role in body's immune response and its ability to recognize tumor cells. This immunotherapy drug may boost body's T-cells to help fight cancer and enhance body's response to cancer.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: NT-I7 for the Treatment of Recurrent Squamous Cell Carcinoma of Head and Neck Undergoing Surgery
  • Official Title: A Window of Opportunity Trial of NT-I7 in Patients With Locally Recurrent Squamous Cell Carcinoma of Head and Neck (SCCHN) Undergoing Salvage Surgery

Clinical Trial IDs

  • ORG STUDY ID: 202014
  • SECONDARY ID: NCI-2020-07340
  • NCT ID: NCT04588038

Conditions

  • Recurrent Head and Neck Squamous Cell Carcinoma
  • Recurrent Hypopharyngeal Squamous Cell Carcinoma
  • Recurrent Laryngeal Squamous Cell Carcinoma
  • Recurrent Oral Cavity Squamous Cell Carcinoma
  • Recurrent Oropharyngeal Squamous Cell Carcinoma
  • Resectable Oropharyngeal Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
Efineptakin alfaGX-I7, Hyleukin-7 (TM), Il-7 Hybrid Fc, IL-7-hyFc, NT-I7, rhIL-7-hyFc, TJ 107, TJ-107, TJ107Treatment (efineptakin alfa)

Purpose

This phase I trial evaluates the side effects of NT-I7 in treating patients with squamous cell carcinoma of head and neck that has come back (recurrent) who are undergoing surgery. NT-I7 is an immunotherapy drug that works by helping the immune system fight tumor cells. The body produces T-cells which play an important role in body's immune response and its ability to recognize tumor cells. This immunotherapy drug may boost body's T-cells to help fight cancer and enhance body's response to cancer.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To evaluate safety and feasibility of a single intramuscular injection of efineptakin alfa
      (NT-I7) in patients with locally recurrent squamous cell carcinoma of head and neck (SCCHN).

      SECONDARY OBJECTIVES:

      I. To describe changes in absolute lymphocyte count (ALC) in peripheral blood after a single
      dose of NT-I7.

      II. To describe changes in tumor infiltrating lymphocytes (TIL) in tumor microenvironment of
      surgical specimen after a single dose of NT-I7.

      III. To evaluate changes in immune subsets in peripheral blood after a single dose of NT-I7
      and after surgery.

      EXPLORATORY OBJECTIVE:

      I. To make assessment of exploratory biomarkers for pharmacodynamic activity of NT-I7 in
      peripheral blood, and/or tumor tissue.

      OUTLINE:

      Patients receive one dose of efineptakin alfa intramuscularly (IM).

      After completion of study treatment, patients are followed up for 35 days after dose or 21
      days after surgery.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (efineptakin alfa)ExperimentalPatients receive one dose of efineptakin alfa IM.
  • Efineptakin alfa

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed squamous cell carcinoma
             of oral cavity, oropharynx, hypopharynx or larynx with recurrent disease which is
             amenable for curative intent surgical resection

          -  Patients must have at least grade 2 lymphopenia at baseline by Common Terminology
             Criteria for Adverse Events (CTCAE) version (v)5.0 criteria (absolute lymphocyte count
             < 800/uL)

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

          -  Absolute neutrophil count >= 1,500/microliter (mcL)

          -  Platelets >= 100,000/mcL

          -  Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) unless elevated due
             to Gilbert's syndrome and direct bilirubin is within normal limits

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) =< 3
             X institutional upper limit of normal

          -  Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT) =< 3 X
             institutional upper limit of normal

          -  Alkaline phosphatase =< 2.5 x ULN (=< 5 x ULN for subjects with documented liver
             involvement or bone metastases)

          -  Creatinine =< 1.5 x within institutional upper limit of normal OR

          -  Creatinine clearance glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2,calculated
             using the Cockcroft-Gault equation, unless data exists supporting safe use at lower
             kidney function values, no lower than 30 mL/min/1.73 m^2

          -  Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral
             therapy with undetectable viral load within 6 months are eligible for this trial

          -  For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
             load must be undetectable on suppressive therapy, if indicated

          -  Individuals with a history of hepatitis C virus (HCV) infection must have been treated
             and cured. For individuals with HCV infection who are currently on treatment, they are
             eligible if they have an undetectable HCV viral load

          -  Individuals with a prior or concurrent malignancy whose natural history or treatment
             does not have the potential to interfere with the safety or efficacy assessment of the
             investigational regimen are eligible for this trial

          -  The effects of NT-I7 on the developing human fetus are unknown. For this reason, women
             of child-bearing potential and men must agree to use adequate contraception for the
             duration of study participation and for 3 months after the study treatment. Should a
             woman become pregnant or suspect she is pregnant while she or her partner is
             participating in this study, she should inform her treating physician immediately

          -  Men treated or enrolled on this protocol must also agree to use adequate contraception
             prior to the study, for the duration of study participation for 3 months after the
             study treatment

        Exclusion Criteria:

          -  Had received immune check point inhibitor within 6 weeks prior to study entry OR
             chemotherapy, radiation therapy or surgery within 4 weeks prior to study entry except
             palliative radiotherapy to non-target lesions (within 2 weeks prior to study entry)

          -  Has history of autoimmune disease which requires active immune suppression (steroid
             replacement for iatrogenic deficiencies, prednisone 5 mg or less [or equivalent dose],
             or topical steroids are allowed)

          -  Is currently receiving any other investigational agents

          -  Has uncontrolled tumor-related pain

          -  Has uncontrolled intercurrent medical illness, including but not limited to congestive
             heart failure, recent acute cardiac event within 6 months, and recent major bleeding
             event within 6 months

          -  Pregnant women are excluded from this study because effects of NT-I7 on developing
             fetus is unknown. Because there is an unknown but potential risk for adverse events in
             nursing infants secondary to treatment of the mother with NT-I7, breastfeeding should
             be discontinued if the mother is treated with NT-I7

          -  Is not recovered from adverse events (AEs) (other than alopecia, vitiligo, neuropathy
             or endocrinopathy managed with replacement therapy) due to agents administered more
             than 4 weeks earlier (i.e., have residual toxicities > grade 1)

          -  Had major surgical procedure, open biopsy, or significant traumatic injury within 4
             weeks prior to study initiation

          -  Had concurrent or previous other malignancy within 5 years of study entry, except
             noninvasive or indolent malignancy

          -  Has spinal cord compression not definitively treated with surgery and/or radiation

          -  Has active autoimmune diseases including but not limited to systemic lupus
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
             associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's
             syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, vasculitis or
             glomerulonephritis

          -  Has active and clinically relevant bacterial, fungal, viral, or Tuberculosis (TB)
             infection, including known Hepatitis A, B, or C or human immunodeficiency virus (HIV)
             (testing not required) or have been hospitalized within 4 weeks prior to NT-I7
             injection
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of treatment-related adverse events
Time Frame:Up to 35 days after the after the NT-I7 injection
Safety Issue:
Description:The proportion of patients experiencing grade 3 or 4 adverse events assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be reported with exact binomial 95% confidence intervals. Safety analyses will be performed for all patients who receive a dose of NT-I7

Secondary Outcome Measures

Measure:Changes in Absolute lymphocyte count (ALC)
Time Frame:Up to 36 days after the NT-I7 injection
Safety Issue:
Description:Descriptive changes in ALC in peripheral blood both before and after a single dose of NT-I7 will be recorded.
Measure:Changes in Tumor infiltrating lymphocytes (TIL)
Time Frame:Up to 15 days after the NT-I7 injection
Safety Issue:
Description:Descriptive changes in tumor infiltrating lymphocytes in tumour microenvironment (TME) after a single dose of NT-I7 in pre-treatment biopsy and surgical specimen will be recorded.
Measure:Changes in immune subsets
Time Frame:Up to 36 days after the NT-I7 injection
Safety Issue:
Description:Descriptive changes in immune subsets in peripheral blood after a single dose of NT-I7 and after surgery as measured by mass cytometry will be recorded.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hyunseok Kang, MD

Last Updated

October 7, 2020