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Efficacy of Interleukin-2 in Triple Negative Breast Cancer

Primary Purpose

Triple Negative Breast Cancer

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Proleukin 1.3 MG Injection
Sponsored by
Gregory Knapp
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Triple Negative Breast Cancer

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Women with biopsy proven TNBC who are not scheduled to receive neoadjuvant chemotherapy. Tumors ≤ 2 cm (clinical T1N0) Planned upfront surgery (patient preference) Medically unable to receive neoadjuvant chemotherapy 18 - 80 years of age. Able to provide consent for the study. Able to come to the hospital for the intralesional injections. Exclusion Criteria: No diagnosis of TNBC. Not able to provide consent for the study. Not able to come to the hospital for study visits. Presence of any contraindication for IL-2 therapy (abnormal thallium stress test, abnormal pulmonary function test, organ allograft and toxicities with a previous dosage). Participant has experienced IL-2 related toxicities during an earlier course of therapy (sustained ventricular tachycardia; cardiac arrythmias unresponsive to management; chest pain with ECG changes consistent with angina or myocardial infarction; cardiac tamponade; intubation required > 72 hours; renal failure requiring dialysis > 72 hours; coma, or toxic psychosis > 48 hours; repetitive or difficult to control seizures; bowel ischemia; gastrointestinal bleeding requiring surgery) If participant is on cancer treatment drugs and steroids to avoid drug interactions. Known pregnancy and breast feeding. There are no known studies to support the use of interleukin in pregnancy and breast-feeding mothers.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Intervention Arm

    Arm Description

    Intralesional IL-2 therapy x 4 weeks between initial consultation and planned surgery

    Outcomes

    Primary Outcome Measures

    Pathologic complete response (pCR) as defined by the residual cancer burden (RCB) index (RCB 0-IV)
    Presence of in-situ disease alone will be considered a pCR

    Secondary Outcome Measures

    Programmed death ligand-1 (PD-L1) and tumor infiltrative lymphocyte (TIL) expression
    Expression of PD-L1 and TIL in each specimen
    Disease free survival
    Overall survival

    Full Information

    First Posted
    November 18, 2022
    Last Updated
    September 7, 2023
    Sponsor
    Gregory Knapp
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05821686
    Brief Title
    Efficacy of Interleukin-2 in Triple Negative Breast Cancer
    Official Title
    Efficacy of Intralesional IL-2 for Resectable Triple Negative Breast Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 2, 2024 (Anticipated)
    Primary Completion Date
    April 2024 (Anticipated)
    Study Completion Date
    April 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Gregory Knapp

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This study is a single arm, non-randomized experimental study design. It will provide us opportunity to conduct a pilot study to evaluate the efficacy of an intralesional immunotherapy (e.g. IL-2) in early stage TNBC as a well-tolerated, low-risk intervention with the potential to improve outcomes without the toxicity of systemic treatment. Following are the objectives of this study: Utilize new and existing infrastructure within the Breast Health and Women Program at the IWK to conduct the institutions first surgery-driven breast cancer trial Evaluate the feasibility of patient accrual in a window of opportunity trial design Evaluate the efficacy of intralesional IL-2 to produce a pathologic response in TNBC. The participants with TNBC will be receiving 3-4 injections of Interleukin-2. Total dose per injection is 25 million international units per mm width of tumor to max dose of 10 million IU. Half of total dose will be injected in the center of lesion/tumor and remaining half of total dose at periphery / peri-tumoral.
    Detailed Description
    Breast cancer is a leading cause of cancer related death in women. Triple negative breast cancer (TNBC) is a subtype of breast cancer based on immunohistochemistry lacks estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor-2 (HER2) expression. It is known to disproportionately affects younger women and women of African ancestry. TNBCs account for approximately 15-20% of all newly diagnosed breast cancer. Compared to other subtypes of breast cancer, including hormone sensitive disease, TNBC is associated with a high risk of distant metastases and is associated with a lower disease-free and overall survival. As TNBCs lack expression for ER, PR and HER-2, targeted therapies are ineffective. Immunotherapy has emerged as an important treatment strategy in TNBC. Traditionally, breast cancer has been considered a 'cold' cancer but the disease is highly heterogenous and TNBC appears to be more immunogenic (i.e. 'hot'). Compared to other forms of the disease, TNBC is associated with a higher mutational burden, tumor infiltrating lymphocytes (TILs) and PD-L1 expression. The later is associated with response to immunotherapy. Indeed, systemic immunotherapy is now approved as first line therapy for metastatic and unresectable PD-L1 positive TNBC. Systemic immunotherapy may also increase the incidence of pathologic complete response after neoadjuvant therapy in early stage TNBC, although the impact on disease-free and overall survival is less clear. Improvement in pathologic complete response is weighed against rare but life-threatening immune related side-effects of immunotherapy, including adrenal insufficiency, pneumonitis causing respiratory arrest and multi-organ dysfunction syndrome. Interleukin-2 is one of the first immunomodulating agents to be approved for cancer treatment, including renal cell carcinoma and melanoma. The cytokine plays an important role in the maintenance CD4+ regulatory T-cells and the differentiation of CD4+ T-cells into a variety of subsets. It also promotes CD8+ T-cell and NK cell cytotoxicity activity and modulates T-cell differentiation in response to antigen presentation. Systemically, IL-2 is limited by a short half-life and significant toxicities. The intralesional injection of IL-2 eliminates the undesirable grade II/III toxicities and often severe side effects of the therapy, while achieving high doses of IL-2 at the tumor site. The most common side effect of intralesional IL-2 is inflammation at the site of injection and mild flu like symptoms, including fatigue and nausea. Rarely patients may experience low-grade fever or headache, which are easily controlled by over-the-counter medications. A number of studies have reported on the use of intralesional IL-2 in management of in-transit melanoma. In this patient population, intralesional IL-2 produces a durable complete response. Much less has been published on its use in other cancers, such as breast cancer. However, there is case report level evidence to suggest that intralesional IL-2 can produce a pathologic complete response in metastatic / unresectable TNBC. The present study considers the significant scope that remains to improve the outcomes for women with TNBC. This study seeks to build upon the growing body of evidence in support of immunomodulation in the treatment of TNBC, while also exploring a different and less toxic route of administration (i.e. intralesional as opposed to systemic). In the window of opportunity between the time of initial surgical consultation and planned OR for patients proceeding with upfront surgery, this study proposes to provide intralesional IL-2 with immediate pathologic assessment. This 'window of opportunity' design will provide us opportunity to conduct a pilot study to evaluate the efficacy of an intralesional immunotherapy (e.g. IL-2) in early stage TNBC as a well-tolerated, low-risk intervention with the potential to improve outcomes without the toxicity of systemic treatment. As systemic immunotherapy moves from the metastatic setting to the adjuvant setting and is increasingly being used in earlier and earlier stage disease, the rationale for systemic therapy with systemic side effects to treat a local disease becomes harder to justify. This study seeks to challenge the notion that the only effective immunotherapy in the treatment of TNBC is systemic and perhaps a local administration can produce the immune response needed to affect significant pathologic response.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Triple Negative Breast Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    10 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Intervention Arm
    Arm Type
    Experimental
    Arm Description
    Intralesional IL-2 therapy x 4 weeks between initial consultation and planned surgery
    Intervention Type
    Drug
    Intervention Name(s)
    Proleukin 1.3 MG Injection
    Intervention Description
    All the recruited participants will receive 4 intra-lesional injections of Interleukin-2 with a dose of 250,000 international units (IU) per mm width of tumor to max dose of 10 million IU.
    Primary Outcome Measure Information:
    Title
    Pathologic complete response (pCR) as defined by the residual cancer burden (RCB) index (RCB 0-IV)
    Description
    Presence of in-situ disease alone will be considered a pCR
    Time Frame
    measured immediately after surgery during routine pathological assessment
    Secondary Outcome Measure Information:
    Title
    Programmed death ligand-1 (PD-L1) and tumor infiltrative lymphocyte (TIL) expression
    Description
    Expression of PD-L1 and TIL in each specimen
    Time Frame
    measured immediately after surgery during routine pathological assessment
    Title
    Disease free survival
    Time Frame
    from time of surgery to 5 years of follow-up
    Title
    Overall survival
    Time Frame
    from time of surgery to 5 years of follow-up

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Women with biopsy proven TNBC who are not scheduled to receive neoadjuvant chemotherapy. Tumors ≤ 2 cm (clinical T1N0) Planned upfront surgery (patient preference) Medically unable to receive neoadjuvant chemotherapy 18 - 80 years of age. Able to provide consent for the study. Able to come to the hospital for the intralesional injections. Exclusion Criteria: No diagnosis of TNBC. Not able to provide consent for the study. Not able to come to the hospital for study visits. Presence of any contraindication for IL-2 therapy (abnormal thallium stress test, abnormal pulmonary function test, organ allograft and toxicities with a previous dosage). Participant has experienced IL-2 related toxicities during an earlier course of therapy (sustained ventricular tachycardia; cardiac arrythmias unresponsive to management; chest pain with ECG changes consistent with angina or myocardial infarction; cardiac tamponade; intubation required > 72 hours; renal failure requiring dialysis > 72 hours; coma, or toxic psychosis > 48 hours; repetitive or difficult to control seizures; bowel ischemia; gastrointestinal bleeding requiring surgery) If participant is on cancer treatment drugs and steroids to avoid drug interactions. Known pregnancy and breast feeding. There are no known studies to support the use of interleukin in pregnancy and breast-feeding mothers.

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    Efficacy of Interleukin-2 in Triple Negative Breast Cancer

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