STRIDE - STimulating Immune Response In aDvanced brEast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Tecemotide (L-BLP25) and Hormonal Treatment; Placebo of tecemotide (L-BLP25) and Hormonal Treatment; cyclophosphamide; sodium chloride (NaCl)
Intervention description: Investigational Arm:
Pretreatment (Single Dose) 300 mg/m^2 of intravenous cyclophosphamide in investigational arm to a maximum of 600 milligrams (mg).
Primary treatment phase:
Hormonal treatment plus 8 consecutive weekly subcutaneous vaccinations with tecemotide (L-BLP25) 1000 micrograms (actual delivered dose was 930 micrograms)* (Week 1 to 8).
Maintenance treatment phase:
Hormonal treatment plus vaccinations with tecemotide (L-BLP25) 1000 micrograms (actual delivered dose was 930 micrograms)* at six-week intervals beginning at Week 14 and continued until Progressive Disease (PD).
*calculated as mass of lipopeptide (antigen); Control Arm:
Pretreatment (Single Dose) NaCl 9 g/L infusion as a substitute for cyclophosphamide.
Primary treatment phase:
Hormonal therapy plus 8 consecutive weekly subcutaneous placebo doses (Week 1 to 8).
Maintenance treatment phase:
Hormonal therapy plus placebo doses at six-week intervals beginning at Week 14 and continued until Progressive Disease (PD).; 300 mg/m^2 (to a maximum of 600 mg) of intravenous cyclophosphamide.; NaCl 9 g/L infusion
Intervention MeSH terms: Cyclophosphamide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 16.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Phase III trial; randomized; cancer vaccine; MUC1; BLP25; advanced breast cancer; postmenopausal breast cancer; immunotherapy of breast cancer; Inoperable locally advanced, recurrent, or metastatic endocrine-sensitive Breast Cancer

Summary:

      EMD Serono has decided to permanently terminate the trial EMR 200038-010 (STRIDE) in the
      indication of breast cancer following the clinical hold on the investigational new drug
      application for tecemotide (L-BLP25).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Postmenopausal women as defined in the protocol

          -  Estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive,
             histologically or cytologically confirmed primary carcinoma of the breast

          -  Expressing at least one of the following five human leukocyte antigen (HLA)
             haplotypes, as centrally assessed by HLA genotyping from whole blood: HLA-A2, -A3,
             -A11, -B7, or -B35

          -  Locally advanced, recurrent, or metastatic breast cancer (Subject must have at least
             one lesion not located in bone)

          -  Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST), and
             inoperable

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Adequate hematologic, hepatic, and renal function within two weeks prior to initiation
             of therapy, as defined by the protocol

          -  Other protocol-defined inclusion criteria may apply

        Exclusion Criteria:

        Disease Status

          -  PD either during hormonal therapy for early breast cancer (adjuvant therapy) or within
             48 months from the initiation of such therapy

          -  Human epidermal growth factor receptor 2-positive (HER2+) breast cancer as defined in
             the protocol

          -  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

          -  Past or current history of malignant neoplasm other than breast cancer (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

          -  Known active Hepatitis B infection or carrier state and/or Hepatitis C infection,
             known Human Immunodeficiency Virus 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

        Pre-therapies

          -  Receipt of immunotherapy (for example [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 (28
             days) 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, or immunotherapy), with the
             exception of hormonal therapy (HT) when given for a period not exceeding 4 weeks (28
             days) prior to randomization, for treatment of 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

        Physiological Function

          -  Central nervous system disease or brain metastases, as documented by computed
             tomography (CT) or magnetic resonance imaging (MRI)

          -  Medical or psychiatric conditions that would interfere with the ability to provide
             informed consent, communicate side effects, or comply with protocol requirements

          -  Clinically significant cardiac disease, e.g., cardiac failure of New York Heart
             Association (NYHA) classes III-IV; uncontrolled angina pectoris, uncontrolled
             arrhythmia, uncontrolled hypertension, or myocardial infarction in the previous six
             months, as confirmed by an electrocardiogram (ECG)

          -  Splenectomy

        Standard Criteria

          -  Need for concurrent treatment with a non-permitted therapy (e.g., concurrent
             chemotherapy, radiotherapy, systemic immunosuppressive drugs, use of herbal medicines
             or botanical formulations intended to treat cancer) while on protocol therapy.
             Palliative radiation to painful bone lesions is allowed

          -  Participation in another clinical study within 30 days prior to randomization

          -  Known hypersensitivity to the study drugs

          -  Known alcohol or drug abuse

          -  Legal incapacity or limited legal capacity

          -  Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family
             members who suffer(ed) from such.

          -  Subject who could be regarded as "vulnerable" according to International Conference on
             Harmonisation (ICH) Good Clinical Practice (GCP) guidelines (e.g., the subject's
             willingness to volunteer in a clinical trial may be unduly influenced by the
             expectation, whether justified or not, of benefits associated with participation, or
             of a retaliatory response from senior members of a hierarchy in case of refusal to
             participate, plus persons kept in detention; persons in nursing homes; subjects in
             emergency situations; homeless persons; and nomads)

          -  Any other reason that, in the opinion of the investigator, precludes the subject from
             participating in this study