A Study of Stimuvax® in Combination With Hormonal Treatment Versus Hormonal Treatment Alone for First-line Therapy of Endocrine-sensitive Advanced Breast Cancer (STRIDE)

Following the clinical hold, EMD Serono has decided to permanently terminate the trial EMR 200038-010 (STRIDE) in the indication of breast cancer.

The purpose of the study is to determine whether the addition of the experimental cancer vaccine Stimuvax to hormonal treatment is effective in prolonging progression-free survival in postmenopausal women with endocrine-sensitive inoperable locally advanced, recurrent or metastatic breast cancer.

• Biological: Stimuvax (L-BLP 25 or BLP25 liposome vaccine) and Hormonal Treatment

  Investigational Arm:

  Pretreatment (Single Dose) 300 mg/m2 of IV cyclophosphamide in investigational arm

  Primary treatment phase:

  Hormonal treatment plus 8 consecutive weekly subcutaneous vaccinations with 1000 µg* L-BLP25 (week 1 to 8)

  Maintenance treatment phase:

  Hormonal treatment plus vaccinations with 1000 µg* L-BLP25 at six-week intervals beginning at week 14 and continued until Progressive Disease (PD)

  *calculated as mass of lipopeptide (antigen)

• Biological: Placebo of Stimuvax (L-BLP 25 or BLP25 liposome vaccine) and Hormonal Treatment

  Control Arm:

  Pretreatment (Single Dose) 0.9% NaCl infusion as placebo

  Primary treatment phase:

  Hormonal therapy plus 8 consecutive weekly subcutaneous vaccinations with Placebo (week 1 to 8)

  Maintenance treatment phase:

  Hormonal therapy plus Vaccinations with Placebo at six-week intervals beginning at week 14 and continued until Progressive Disease (PD)

• Drug: cyclophosphamide
  300 mg/m2 of IV cyclophosphamide
• Drug: sodium chloride
  0.9% sodium chloride infusion

• Experimental: Investigational Arm

  Investigational Arm:

  • Pretreatment (Single Dose): 300 mg/m2 of IV cyclophosphamide
  • L-BLP25 plus Hormonal Therapy (Standard Dose)
  Interventions:

  • Biological: Stimuvax (L-BLP 25 or BLP25 liposome vaccine) and Hormonal Treatment
  • Drug: cyclophosphamide
• Active Comparator: Control Arm:

  Control Arm:

  • Pretreatment (Single Dose): 0.9% sodium chloride infusion
  • Placebo plus Hormonal Therapy (Standard Dose)
  Interventions:

  • Biological: Placebo of Stimuvax (L-BLP 25 or BLP25 liposome vaccine) and Hormonal Treatment
  • Drug: sodium chloride

Inclusion Criteria:

• Postmenopausal women
• ER+ and/or PgR+, histologically or cytologically confirmed primary carcinoma of the breast
• 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 breast cancer (Subject must have at least one lesion not located in bone).
• Measurable disease by RECIST, and inoperable
• 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

Exclusion Criteria:

Disease Status

• PD either during hormonal therapy for early breast cancer (adjuvant therapy) or within 12 months of completing such therapy
• Human epidermal growth factor receptor 2-positive (HER2+) breast cancer
• 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 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 (28 days) prior to randomization. Note: Subjects who have received monoclonal antibodies for imaging are eligible.
• 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)
• 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.