Clinical Trials /

Evaluation of Pharmacodynamic Effects of IT-pIL12-EP in Patients With TNBC

NCT02531425

Description:

Intratumoral plasmid IL-12 electroporation (IT-pIL12-EP) will be administered to approximately 10 patients with triple negative breast cancer (TNBC) with cutaneous or subcutaneous disease. Patients will receive one complete cycle of therapy, consisting of local injection of plasmid IL-12 (pIL-12) followed immediately by electroporation (EP), into accessible tumor lesions. IT-pIL12-EP will be administered in Days 1, 5, and 8 of the single 28-day cycle.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Evaluation of Pharmacodynamic Effects of IT-pIL12-EP in Patients With TNBC

Title

  • Brief Title: Evaluation of Pharmacodynamic Effects of IT-pIL12-EP in Patients With TNBC
  • Official Title: Evaluation of Pharmacodynamic Effects of Intratumoral Delivery of Plasmid IL-12 Electroporation in Patients With Triple Negative Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02531425

    ORG ID: OMS-I140

    Trial Conditions

    ER-Negative PR-Negative HER2-Negative Breast Cancer

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    Intratumoral plasmid IL-12 electroporation (IT-pIL12-EP) will be administered to
    approximately 10 patients with triple negative breast cancer (TNBC) with cutaneous or
    subcutaneous disease. Patients will receive one complete cycle of therapy, consisting of
    local injection of plasmid IL-12 (pIL-12) followed immediately by electroporation (EP), into
    accessible tumor lesions. IT-pIL12-EP will be administered in Days 1, 5, and 8 of the
    single 28-day cycle.

    Detailed Description

    This pilot study will evaluate the pharmacodynamic effects of intratumoral injection of
    pIL-12 followed immediately by electroporation (IT-pIL12-EP). A minimum of ten patients
    with biopsy-accessible triple negative breast cancer (TNBC) will be treated in this study.
    Additional patients, up to a maximum of 25 patients, may be enrolled based upon
    pharmacodynamic observations and at the discretion of the Principal Investigator, in
    consultation with the Sponsor. All patients will receive a single 28-day treatment cycle.
    One lesion will remain untreated (the control lesion). Treatment will be administered on
    Days 1,5, and 8 of the single 28-day cycle. Treatments will consist of direct injection of
    pIL-12 into tumor lesions, followed immediately by electroporation of the lesions. At the
    end of the treatment cycle, patients will return to clinic for a final safety evaluation and
    tumor biopsy. This end of study (EOS) visit will occur prior to initiating any new
    anti-cancer therapy/regimen.

    All patients will undergo tumor biopsies at two separate timepoints for molecular and
    histological analyses associated with the primary endpoint. At least one lesion will be
    biopsied at Screening (pre-treatment sample). Biopsies of the untreated control lesion and
    at least one treated lesion will be obtained at the EOS visit (post-treatment samples).
    Additional tumor biopsy samples may be requested if there is either tumor regression or
    progression prior to EOS.

    Duration of participation will be approximately 4 weeks for each patient. A patient is
    considered to have completed the study if all three IT-pIL12-EP treatments (Days 1, 5, & 8)
    and all required pre- and post-treatment tumor biopsies have been obtained and EOS safety
    follow-up evaluations have been performed.

    Trial Arms

    Name Type Description Interventions
    IT-pIL12-EP Experimental intratumoral injection of plasmid-IL12 following immediately by electroporation

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically confirmed diagnosis of locally-advanced, inoperable, metastatic and/or
    treatment-refractory triple negative breast cancer (TNBC). Patients must have both
    ER and PR staining < 5% and be HER2-negative.

    - Age 18 years.

    - ECOG Performance Status of 0-1.

    - Life expectancy 6 months.

    - Patients may have had radiation therapy, but must have progressive disease after
    radiation therapy if the lesions to be treated are within the radiation field.
    Radiation treatment must be completed 4 weeks prior to Cycle 1 Day 1.

    - Adequate hepatic function with total bilirubin and ALT < 1.5X the upper limit of
    normal (ULN), except in patients with Gilbert's Syndrome must have a total bilirubin
    < 3X ULN and ALT < 3X ULN. In cases of known liver metastases, ALT 5X ULN is
    acceptable (total bilirubin must be < 1.5X ULN).

    - Adequate renal function, estimated or calculated creatinine clearance of > 50 mL/min
    (calculated using the formula of Cockcroft and Gault) -or- serum creatinine 2.0
    mg/dL.

    - Adequate hematological function, defined as ANC 1,500/mm3, Hb 9.0 g/dL, and
    platelet count 100,000/mm3.

    - Lesions that are accessible for injection and electroporation, defined as cutaneous
    or subcutaneous disease.

    - At least 2 anatomically distinct lesions accessible for biopsy.

    - Must consent to study-specific biopsies at two separate timepoints: pre-treatment
    (Screening) and post-treatment (Day 28 or EOS).

    - Tumor lesions in the CNS are permitted but lesions must have been stable for at least
    3 months prior to Cycle 1 Day 1 (C1D1). Stable CNS lesions are defined as not
    requiring steroid prophylaxis or other medications to prevent seizures or other
    complications associated with CNS lesions and no evidence of worsening of CNS
    disease.

    - Female patients of childbearing potential must have a negative serum or urine
    pregnancy test within 3 days prior to C1D1 and agree to use dual methods of
    contraception during the study and for a minimum of 30 days following the last
    treatment. Post menopausal females (>45 years old and without menses for > 1 year)
    and surgically sterilized females are exempt from these requirements.

    Male patients must use an effective barrier method of contraception during the study and
    for a minimum of 30 days following the last treatment if sexually active with a female of
    childbearing potential.

    - Resolution of all treatment-related toxicities, except alopecia, anemia and
    neuropathy, from any previous cancer therapy to Grade 1 prior to the first dose of
    study treatment.

    - Ability to provide written informed consent.

    Exclusion Criteria:

    - Any other current or previous malignancy within the past three years that, in the
    opinion of the Principal Investigator, will interfere with study-specific objectives.

    - Patients with electronic pacemakers or defibrillators.

    - Chemotherapy or hormonal therapy for anti-cancer treatment within 28 days prior to
    Cycle 1 Day 1.

    - Immunotherapy or biological therapy (e.g., monoclonal antibodies) within 28 days
    prior to Cycle 1 Day 1, unless pre-approval is obtained from the Sponsor Medical
    Monitor.

    - Treatment with unapproved investigational therapeutic agent within 28 days prior to
    Cycle 1 Day 1, unless pre-approval is obtained from the Sponsor Medical Monitor.

    - Patients receiving systemic steroid therapy for a chronic inflammatory condition
    (e.g., rheumatoid arthritis, Crohn's Disease, etc.). Topical steroids are also
    excluded. Nasal and inhaled steroids are permitted.

    - Unstable/inadequate cardiac function:

    - symptomatic ischemia

    - uncontrolled or clinically significant conduction abnormalities; first degree AV
    block or asymptomatic LAFB/RBBB are eligible

    - myocardial infarction in the previous six months

    - congestive heart failure (New York Heart Association class III to IV)

    - Major surgery within 28 days prior to C1D1.

    - Infection requiring parenteral antibiotics, antivirals, or antifungals within 2 weeks
    prior to C1D1.

    - Patients who are known to have HIV infection/seropositivity.

    - Active Hepatitis A, B, or C infection or known to be positive for HCV RNA or HBV
    surface antigen without vaccination.

    - Serious psychiatric or medical conditions that could interfere with treatment or
    protocol-related procedures.

    - Patients who are pregnant or lactating.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Changes in the proportion of intratumoral lymphocyte subsets

    NanoString-based gene expression

    Secondary Outcome Measures

    Number of Participants with Treatment-Related Adverse Events as assessed by the CTCAE v4.0

    Anti-tumor activity

    Detection of plasmid IL-12 in untreated lesions

    Trial Keywords

    TNBC

    Triple Negative Breast Cancer