Description:
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.
Title
- Brief Title: Talimogene Laherparepvec in Treating Patients With Recurrent Breast Cancer That Cannot Be Removed by Surgery
- Official Title: A Phase II Study Using Talimogene Laherparepvec for Inflammatory Breast Cancer (IBC) or Non-IBC Patients With Inoperable Local Recurrence
Clinical Trial IDs
- ORG STUDY ID:
2014-0034
- SECONDARY ID:
NCI-2016-00199
- SECONDARY ID:
2014-0034
- SECONDARY ID:
P30CA016672
- NCT ID:
NCT02658812
Conditions
- Malignant Chest Wall Neoplasm
- Recurrent Breast Carcinoma
- Recurrent Inflammatory Breast Carcinoma
- Stage IV Breast Cancer AJCC v6 and v7
- Stage IV Inflammatory Breast Carcinoma
Interventions
Drug | Synonyms | Arms |
---|
Talimogene Laherparepvec | 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 | Treatment (talimogene laherparepvec) |
Purpose
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.
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.
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment (talimogene laherparepvec) | Experimental | 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. | |
Eligibility Criteria
Inclusion Criteria:
- Histological confirmation of breast carcinoma
- Histological confirmation of recurrence of chest wall with or without distant
metastasis disease
- Patients must have failed at least 1 systemic regimen or have clinical stable disease
with capecitabine, hormonal therapy (with or without mTOR inhibitor or CDK4/6
inhibitor), or anti HER-2 therapy (trastuzumab, pertuzumab, ado-trastuzumab emtansine,
lapatinib) for at least 2 months after their diagnosis of locoregional/metastatic
disease
- Concurrent radiation therapy is permitted after the study treatment is initiated so
long as the planned radiation field doesn't overlap with planned injection sites
- Eastern cooperative oncology group performance status (ECOG PS) 0-1
- Absolute neutrophil count (ANC) >= 1.0 x 10^9/L; if patient is taking CDK4/6 inhibitor
or capecitabine, there is a need for maintaining ANC >= 1.0 consistently for at least
2 months without dose changes
- Platelet count >= 75 x 10^9/L, if patient is taking CDK4/6 inhibitor, ado-trastuzumab
emtansine or capecitabine, there is a need for maintaining platelet count >= 75 x
10^9/L without dose changes
- Hemoglobin >= 8.0 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
- Serum creatinine =< 1.5 x upper limit of normal (ULN), OR 24-hour creatinine clearance
>= 60 mL/min for subject with creatinine levels > 1.5 x ULN; (Note: creatinine
clearance need not be determined if the baseline serum creatinine is =< 1.5 x ULN;
creatinine clearance should be determined per institutional standard)
- Aspartate aminotransferase (AST) =< 2.5 x ULN if liver metastases present
- Alanine aminotransferase (ALT) =< 2.5 x ULN if liver metastases present
- Total bilirubin =< 1.5 x ULN, OR direct bilirubin =< ULN for a subject with total
bilirubin level > 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 except capecitabine or
ado-trastuzumab emtansine, immunotherapy) while taking study medication, or have
previously received talimogene laherparepvec or any other oncolytic virus
- Patients with metastatic sites that requires chemotherapy (except capecitabine or
ado-trastuzumab emtansine)
- 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;
the exception does not include carcinomatosis meningitis which is excluded regardless
of clinical stability
- More than three lesions per organ for visceral metastases except for lung or lymph
node sites
- History or evidence of active autoimmune disease that has required systemic treatment
(i.e., use of corticosteroids, immunosuppressive drugs or disease modifying agents);
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 other malignancy within the past 5 years with the following exceptions: a)
Adequately treated non melanoma skin cancer without evidence of disease at the time of
enrollment b). Adequately treated cervical carcinoma in situ without evidence of
disease at the time of enrollment c). Adequately treated breast ductal carcinoma in
situ without evidence of disease at the time of enrollment d). Prostatic
intraepithelial neoplasia without evidence of prostate cancer at the time of
enrollment
- Patients with active infection and requiring intravenous (IV) or oral antibiotics
- Evidence of immune suppression as following:
- Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency
syndrome (AIDS)
- Known leukemia or lymphoma
- Primary immunodeficiency state such as severe combined immunodeficiency disease
- Concurrent opportunistic infection
- Receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid
doses > 10 mg/day of prednisone or equivalent within 7 days prior to the
initiation of study treatment
- 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 for investigational drugs, procedures or
device (excluding non-cancer treatment trials) or receipt of an investigational agent
or device within 4 weeks of the initiation of study treatment
- 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)
- Prior therapy with tumor vaccine, or received live vaccine within 28 days prior to the
initiation of study treatment
- Subjects who are unwilling to minimize exposure with his/her blood or other body
fluids to individuals who are at higher risks for HSV-1 induced complications such as
immunosuppressed individuals, individuals known to have HIV infection, pregnant women,
or infants under the age of 3 months, during talimogene laherparepvec treatment and
through 30 days after the last dose of talimogene laherparepvec
- Prior immunosuppressive, chemotherapy, radiotherapy (in which the field encompassed a
planned injection site), biological cancer therapy (monoclonal antibodies), or major
surgery within 28 days prior to enrollment or has not recovered to Common Terminology
Criteria for Adverse Events (CTCAE) grade 1 or better from adverse event due to cancer
therapy administered more than 28 days prior to enrollment
- Prior radiotherapy in which the field does not overlap the injection sites or
non-immunosuppressive targeted therapy within 14 days prior to enrollment or has not
recovered to CTCAE grade 1 or better from adverse event due to cancer therapy
administered more than 14 days prior to enrollment
- Patients who have extensive skin disease, defined as total area of skin involvement/
lesions that comprise > 10% of body surface area; skin involvement comprising > 5% to
upper anterior chest wall or > 5% to upper posterior back is excluded
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall response rate defined as the percentage of complete response, partial response in overall patients |
Time Frame: | Up to 5 months |
Safety Issue: | |
Description: | The trial will be conducted using a two-stage design and the overall response rate will be estimated accordingly. |
Secondary Outcome Measures
Measure: | Overall disease control rate |
Time Frame: | Up to 1 year |
Safety Issue: | |
Description: | |
Measure: | Local overall response rate |
Time Frame: | Up to 1 year |
Safety Issue: | |
Description: | |
Measure: | Local disease control rate |
Time Frame: | Up to 1 year |
Safety Issue: | |
Description: | |
Measure: | Progression-free survival |
Time Frame: | Up to 1 year |
Safety Issue: | |
Description: | |
Measure: | Overall survival |
Time Frame: | Up to 1 year |
Safety Issue: | |
Description: | |
Measure: | Incidence of adverse events |
Time Frame: | Up to 1 year |
Safety Issue: | |
Description: | Will be evaluated according to Common Terminology Criteria for Adverse Events version 4.0. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | M.D. Anderson Cancer Center |
Last Updated
June 11, 2020