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Inflammatory Breast Neoplasms

Neoplasms, Glandular and Epithelial

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Breast Diseases

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Inflammatory Breast Cancer

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Talimogene laherparepvec

Antineoplastic Agents, Immunological

Patients receive talimogene laherparepvec IT on day 1. Cycles repeat every 3 weeks in cycle 1 and every 2 weeks thereafter in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Talimogene Laherparepvec

Naoto T Ueno

This phase II trial studies how well talimogene laherparepvec works in treating patients with breast cancer that has come back and cannot be removed by surgery. Biological therapies, such as talimogene laherparepvec, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing.

PRIMARY OBJECTIVES:

I. To determine the efficacy of talimogene laherparepvec in inflammatory breast cancer or non-inflammatory breast cancer patients with inoperable local recurrence measured by the overall response rate.

SECONDARY OBJECTIVES:

I. To determine the efficacy of talimogene laherparepvec in inflammatory breast cancer or non-inflammatory breast cancer patients with inoperable local recurrence measured by the overall disease control rate.

II. To determine the rate of local overall response and disease control rate, progression-free survival (PFS), and overall survival (OS) in all patients.

III. To determine the rate of local overall response and disease control rate, PFS, and OS in patients without distant metastases.

IV. To determine the rate of local overall response and disease control rate, PFS, and OS in patients with distant metastases.

V. To determine the safety of talimogene laherparepvec injection to local disease.

CORRELATIVE STUDIES:

I. To determine the effect of talimogene laherparepvec on injection sites and distant metastatic sites by evaluating immune function and apoptosis with immune cell surface markers and cytokines.

II. To assess changes in the following: serum or plasma levels of interleukin (IL)-2, IL-12, tumor necrosis factor (TNF)-alpha, and interferon (IFN)- alpha; (Reuben's Lab); phenotype for T-cell subsets (CD3, CD4, CD8, CD25) and natural killer cell (NK-cell) subsets (CD16, CD56), which will be determined via multiparameter fluorescence-activated cell sorting (FACS) analysis (percentage and absolute numbers) in peripheral blood at Dr. James Reuben's laboratory of MD Anderson; serum analysis of herpes simplex virus (HSV) type 1 serology with immunoglobulin (Ig)G and IgM (enzyme-linked immunosorbent assay \[ELISA\]).

III. To assess distant tumor tissue changes by evaluating necrosis and immune cell infiltration (T-/B-/NK-Cell, macrophage, dendritic cell) by immunohistochemistry assay (CD3, CD4, CD8, CD20, CD16, CD56, granzyme B, cleaved caspase 3, and Ki-67) when distant tumor sample is obtained; if the sample volume is ample, additional immunohistochemistry assays will be performed for CD45RO, TIA-1, FoxP3, CD25, OX-40, CD57, CD1a, CD208, myeloperoxidase, CD68, COX-2, major histocompatibility complex (MHC) class I and MHC class II in Dr. Savitri Krishnamurthy's laboratory at MD Anderson.

OUTLINE:

Patients receive talimogene laherparepvec intratumorally (IT) on day 1. Cycles repeat every 3 weeks in cycle 1 and every 2 weeks thereafter in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 1 year.

Talimogene Laherparepvec in Treating Patients With Recurrent Breast Cancer That Cannot Be Removed by Surgery

A Phase II Study Using Talimogene Laherparepvec for Inflammatory Breast Cancer (IBC) or Non-IBC Patients With Inoperable Local Recurrence

Overall Response Rate defined as the rate of patients who achieved a partial response or complete response as the best response for the measurable and nonmeasurable disease. Evaluated using RECIST ver.1.1. Complete Response (CR): Disappearance of all target and non-target lesions at a minimum of 4 weeks. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of the target lesions at a minimum of 4 weeks, taking as a reference the baseline sum of the longest diameter with target.

Progressive disease is measured based on Response Evaluation Criteria (RECIST v1.1) beyond 10 cycles. Uncontrolled disease progression is defined as rapid growth of multiple measurable or non-measurable new lesions or sum of the longest diameter of existing targeted lesions is \>40% from the baseline.

Overall survival is defined as the time from treatment initiation until death. Estimated using the Kaplan-Meier method with 95% confidence intervals (CIs).

The number of Grade 2 or higher adverse events possibly, probably, or definitely related to T-VEC. Evaluated according to Common Terminology Criteria for Adverse Events version 4.0.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Grade 2 or higher non-hematologic AEs and grade 3 or higher hematologic AEs will be recorded upon observation by the investigator or reported by the patient (regardless of whether they are attributed to investigational product), documented in the patient's medical record, and recorded in CORe. Grade 2 or higher abnormal lab values will be recorded as AEs; and grade 1 abnormal laboratory values will not be recorded as AEs.

Patients receive talimogene laherparepvec IT on day 1. Cycles repeat every 3 weeks in cycle 1 and every 2 weeks a total of at least 10 cycles, thereafter in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Talimogene Laherparepvec: Given IT

Spots Global Cancer Trial Database for recurrent inflammatory breast carcinoma