Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05821686 |
| Other study ID # |
IL-2.001 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
January 2, 2024 |
| Est. completion date |
April 2025 |
Study information
| Verified date |
November 2023 |
| Source |
Nova Scotia Health Authority |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This study is a single arm, phase II pilot design. The study will evaluate the safety and
efficacy of intralesional immunotherapy (e.g. IL-2) in early stage TNBC. The overall
objective of the research study is to advance our knowledge of novel immunotherapies and
routes of administration for the treatment of TNBC
HYPOTHESES: Neoadjuvant treatment of TNBC with intralesional IL-2 is safe and well tolerated
and can produce a pathological response.
Aim 1: Examine the safety and possible efficacy of a novel neoadjuvant intralesional
intervention (IL-2) for patients with early-stage TNBC.
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 an immunohistochemistry that 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.
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.
