A randomized, double-blind, controlled phase III study of Stimuvax® (L-BLP25 or BLP25 liposome vaccine) in combination with hormonal treatment versus hormonal treatment alone for first-line therapy of post-menopausal women with estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive, inoperable locallyadvanced, recurrent, or metastatic breast cancerSTRIDE - STimulating immune Response In aDvanced brEast cancer - STRIDE

Conditions: post-menopausal women with estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive, inoperable locally advanced, recurrent, or metastatic breast cancer
MedDRA version: 9.1Level: PTClassification code 10055113Term: Breast cancer metastatic

Registration Number: EUCTR2008-005544-17-BE

Lead Sponsor: Merck KGaA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 1200

Inclusion Criteria

For inclusion in the study, all of the following inclusion criteria must be fulfilled:
• Written informed consent given before any study-related activities are carried out
• Female inpatient or outpatient
• = 18 years of age
• Postmenopausal, defined by at least one (1) of the following:
?? No spontaneous menses for at least five years
?? Spontaneous menses within the past five years but amenorrheic for at least
12 months and luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
within the postmenopausal normal range (Subjects who are amenorrheic
following a hysterectomy but who have not had bilateral salpingo-oophorectomy
are not eligible unless they have additional biochemical evidence of menopause as
reflected by ovarian suppression and FSH and plasma estradiol levels in the
postmenopausal range.)
?? Prior bilateral oophorectomy
?? Prior bilateral ovarian irradiation and castration, amenorrheic for at least three
months, and FSH levels > 40 IU/L
?? No menstrual period for 12 months or longer and a serum estradiol level in the
postmenopausal range (= 22 pg/mL)
• ER+ and/or PgR+, histologically or cytologically confirmed primary carcinoma of
the breast (institutional pathological diagnosis of BRCA is acceptable)
• Expressing at least one of the following five HLA haplotypes, as centrally assessed
by HLA genotyping from whole blood: HLA-A2, -A3, -A11, -B7, or -B35
• Locally advanced, recurrent, or metastatic BRCA (Subject must have at least one
lesion not located in bone).
• Measurable disease by RECIST, and inoperable (not eligible for breast-conserving
surgery or mastectomy) with no reasonable expectation of surgery for cure now or in
the future.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of at least 12 weeks
• Adequate hematologic, hepatic, and renal function within two weeks prior to
initiation of therapy, as defined by the following:
?? White blood cells (WBCs) = 2500/mm3; absolute neutrophils = 1500/mm3;
platelets = 100,000/mm3
?? Hemoglobin = 9 g/dL
?? Bilirubin = 1.5 × the upper limit of normal (ULN), or = 5 × ULN in case of
hepatic metastasis
?? Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
= 2.5 × ULN, or = 5 × ULN in case of hepatic metastasis
?? Creatinine = 1.5 × ULN
?? International Normalized Ratio (INR), prothrombin time (PT), and partial
thromboplastin time (PTT) in the normal range
• Willingness to comply with study protocol requirements
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects are not eligible for this study, if they fulfill one or more of the following
exclusion criteria:
Disease Status
• PD either during HT for early breast cancer (adjuvant therapy) or within 12 months
of completing such therapy
• Human epidermal growth factor receptor 2-positive (HER2+) BRCA, defined as
follows:
?? Immunohistochemistry (IHC) staining of 3+ (uniform, intense membrane staining
of > 30% of invasive tumor cells), or
?? Fluorescent in situ hybridization (FISH) result > 6 HER2 gene copies per nucleus,
or
?? FISH ratio (HER2 gene signals to chromosome 17 signals) > 2.2.
Historical data will routinely be confirmed by local pathology laboratories in case
of equivocal” historical results as follows:
o By validated FISH-test if HER2 protein expression is equivocal (i.e.,
IHC 2+) or, if appropriate
o By validated IHC if HER2 gene amplification is equivocal” (i.e.,
FISH ratio 1.8-2.2 or HER2 gene copy 4.0-6.0)
• Autoimmune disease that in the opinion of the investigator could compromise the
safety of the subject in this study. (Exception will be granted for well-controlled
Type I diabetes mellitus.)
• Recognized immunodeficiency disease, including cellular immunodeficiencies,
hypogammaglobulinemia or dysgammaglobulinemia; hereditary or congenital
immunodeficiencies
• Known active hepatitis B infection or carrier state and/or hepatitis C infection,
known human immunodeficiency virus (HIV) infection, or any other infectious
process that in the opinion of the investigator could compromise the subject’s ability
to mount an immune response, or could expose her to the likelihood of more and/or
severe side effects
• Past or current history of malignant neoplasm other than BRCA, except for
curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix, or
other cancer curatively treated and with no evidence of disease for at least five years
Pre-therapies
• Receipt of immunotherapy (e.g., interferons; tumor necrosis factor; interleukins;
growth factors granulocyte macrophage-colony stimulating factor [GM-CSF],
granulocyte-colony stimulating factor [G-CSF], macrophage-colony stimulating
factor [M-CSF], or monoclonal antibodies), or chemotherapy, within four weeks (28days) prior to randomization. Note: Subjects who have received monoclonal
antibodies for imaging are eligible.
• Prior receipt of investigational systemic drugs (including off-label use of approved
products) or any kind of systemic treatment (chemotherapy, HT, or immunotherapy)
for inoperable, locally advanced, recurrent, or metastatic breast cancer
• Prior radiotherapy to the site of cancer, if only one site will be used for evaluation of tumor response.
Prior use of bisphosphonates or concurrent use while on study treatment is allowed.