E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
post-menopausal women with estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive, inoperable locally advanced, recurrent, or metastatic breast cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10055113 |
E.1.2 | Term | Breast cancer metastatic |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Demonstration of superior efficacy (as measured by PFS time) of L-BLP25 in combination with hormonal treatment (HT) over placebo plus HT, when used for first-line therapy of hormone receptor-positive (ER+ and/or PgR+), inoperable locally advanced, recurrent, or metastatic breast cancer (BRCA). |
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E.2.2 | Secondary objectives of the trial |
Secondary • Safety and Tolerability; • Overall Survival (OS) Time; • Objective Tumor Response; • Duration of Response; • Clinical Benefit; • Time to Progression (TTP); • Time to Chemotherapy; • Quality of Life (QOL); • Healthcare Resource Utilization (HRU); • Serum CA 15-3. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in this study is PFS time. For this study, all HTs for front-line therapy of advanced BRCA were approved based on surrogate endpoints (either response rate, response rate and TTP, or TTP). In current guidelines, PFS time is often preferred over TTP as a surrogate endpoint in oncology studies. As PFS time is also considered an acceptable endpoint in situations where subsequent therapies may have an impact on OS time, PFS time was chosen as the primary endpoint of this study. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 90 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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See protocol section 5.1.1 (page 40) If the study is not terminated for a reason given in the protocol section 5.3.3.3, the study will end when each of the following is fulfilled: • The last subject has received the last dose of study medication, and has undergone a 6-week safety follow-up. • The study objectives have been answered. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |