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

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ClinicalTrials.gov Identifier: NCT02658812
Recruitment Status : Active, not recruiting
First Posted : January 20, 2016
Last Update Posted : November 6, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Malignant Chest Wall Neoplasm Recurrent Breast Carcinoma Recurrent Inflammatory Breast Carcinoma Stage IV Breast Cancer AJCC v6 and v7 Stage IV Inflammatory Breast Carcinoma Other: Laboratory Biomarker Analysis Biological: Talimogene Laherparepvec Phase 2

Detailed Description:

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.

TERTIARY OBJECTIVES:

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. Courses repeat every 3 weeks in course 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study Using Talimogene Laherparepvec as a Single Agent for Inflammatory Breast Cancer (IBC) or Non-IBC Patients With Inoperable Local Recurrence
Actual Study Start Date : August 1, 2016
Estimated Primary Completion Date : August 1, 2021
Estimated Study Completion Date : August 1, 2021


Arm Intervention/treatment
Experimental: Treatment (talimogene laherparepvec)
Patients receive talimogene laherparepvec IT on day 1. Courses repeat every 3 weeks in course 1 and every 2 weeks thereafter in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Talimogene Laherparepvec
Given IT
Other Names:
  • ICP34.5-, ICP47-deleted Herpes Simplex Virus 1 (HSV-1) Incorporating the Human GM-CSF Gene
  • Imlygic
  • JS1 34.5-hGMCSF 47- pA-
  • T-VEC




Primary Outcome Measures :
  1. Overall response rate defined as the percentage of complete response, partial response in overall patients [ Time Frame: Up to 5 months ]
    The trial will be conducted using a two-stage design and the overall response rate will be estimated accordingly.


Secondary Outcome Measures :
  1. Overall disease control rate [ Time Frame: Up to 1 year ]
  2. Local overall response rate [ Time Frame: Up to 1 year ]
  3. Local disease control rate [ Time Frame: Up to 1 year ]
  4. Progression-free survival [ Time Frame: Up to 1 year ]
  5. Overall survival [ Time Frame: Up to 1 year ]
  6. Incidence of adverse events [ Time Frame: Up to 1 year ]
    Will be evaluated according to Common Terminology Criteria for Adverse Events version 4.0.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histological confirmation of breast carcinoma
  • Histological confirmation of recurrence of chest wall with or without distant metastasis disease
  • Patients may have any molecular status (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]) and must have failed at least 1 systemic regimen after their diagnosis of locoregional disease
  • Previous adjuvant endocrine therapy for initial breast cancer was allowed but had to be discontinued at least 1 week before receiving the study drug
  • Previous chemotherapy for local recurrence is allowed but must have been discontinued at least 4 weeks before receiving the study drug and the patient must have recovered from acute adverse effects
  • Previous radiation therapy was allowed but must have been discontinued at least 2 months before study drug is administered, and the patient must have recovered from acute toxic effects
  • Eastern cooperative oncology group performance status (ECOG PS) 0-1
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Platelet count >= 100 x 10^9/L
  • Hemoglobin >= 10.0 g/L
  • International normalization ratio (INR) or prothrombin time (PT) 1.5 x upper limit of normal (ULN), unless the subject is receiving anticoagulant therapy, in which case PT and partial thromboplastin time (PTT)/ activated PTT (aPTT) must be within therapeutic range of intended use of anticoagulants
  • Calculated creatinine clearance > 30 ml/min
  • Aspartate aminotransferase (AST) =< 2.5 x ULN
  • Alanine aminotransferase (ALT) =< 2.5 x ULN
  • Total bilirubin =< 1.5 x ULN
  • Subjects must be candidate for intralesional injection into cutaneous, subcutaneous or nodal tumors with or without image ultrasound guidance defined as one or more of the following at least 1 injectable lesion >= 5 mm in longest diameter, multiple injectable lesions that in aggregate have a longest diameter of >= 5 mm
  • Female patients of childbearing potential must have negative urine pregnancy test no more than 3 days prior to starting study treatment
  • Patients must be able and willing to give written informed consent

Exclusion Criteria:

  • Patients who have operable disease with curable intent, and/or are candidates for radiation therapy for local control
  • Patients receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, radiation therapy, hormonal therapy, and biological therapy) while taking study medication or have previously received talimogene laherparepvec or any other oncolytic virus
  • Patients with metastatic sites that requires chemotherapy and/or non-hormonal targeted therapy
  • Known active central nervous metastases; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids > 10 mg/day pf prednisone or equivalent
  • More than three lesions per organ for visceral metastases except for lung or lymph node sites
  • History or evidence of symptomatic autoimmune disease (eg, pneumonitis, glomerulonephritis, vasculitis, or other), or history of active autoimmune disease that has required systemic treatment (ie, use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) in past 2 months prior to enrollment; replacement therapy (eg, thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment for autoimmune disease
  • Patients with concurrent disease or condition that would make them inappropriate for study participation, or any serious medical disorder that would interfere with patients' safety
  • History of a second cancer, except treated basal cell or squamous cell skin cancer, in situ cervical cancer or other cancers for which patients are disease free for at least 3 years
  • Patients with initial diagnoses of stage IV disease
  • Patients with active infection and requiring intravenous (IV) or oral antibiotics
  • Evidence of immune suppression due to:

    • Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)
    • Known leukemia or lymphoma
    • Those who require high dose steroids or other immunosuppressive agents
    • Known hepatitis B or C infection
    • Congenital or acquired cellular and/or humoral immune deficiency
    • Other signs or symptoms of immune system suppression
  • Active herpetic skin lesions or prior complication of herpes simplex virus (HSV)-1 infections (e.g. herpetic encephalitis or keratitis)
  • Currently pregnant or breast-feeding, or planning to become pregnant during study treatment and through 3 months after the last dose of study treatment
  • Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception during study treatment and through 3 months after the last dose of talimogene laherparepvec; (women of not childbearing potential: post-menopausal [age > 55 years with cessation of menses > 12 months or < 55 years but not spontaneous menses for at least 2 years or < 55 years and spontaneous menses within the past 1 year, but currently amenorrheic (eg, spontaneous or secondary to hysterectomy), and with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved] or who have had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy)
  • Sexually active subjects and their partners unwilling to use male or female latex condom to avoid potential viral transmission during sexual contact while on treatment and within 30 days after treatment with talimogene laherparepvec
  • Currently enrolled in another clinical trial (exclude non-cancer treatment trial) or received an investigational agent within 4 weeks of study initiation
  • Requires intermittent or chronic treatment with antiherpetic drugs, except for topical agents
  • Patients who are known sensitive to any of the products or components to be administered during treatment with talimogene laherparepvec
  • Chronic oral or systemic steroid medication use at a dose of > 10 mg/d of prednisone or equivalent (steroids with low systemic absorption [e.g. triamcinolone hexacetonide] injected into joint space are allowed)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02658812


Locations
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Naoto Ueno M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02658812     History of Changes
Other Study ID Numbers: 2014-0034
NCI-2016-00199 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2014-0034 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: January 20, 2016    Key Record Dates
Last Update Posted: November 6, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma
Breast Neoplasms
Inflammatory Breast Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases