STRIDE - STimulating Immune Response In aDvanced brEast Cancer

Phase 3

Terminated

Conditions: Breast Cancer

Interventions: Biological: Placebo of tecemotide (L-BLP25) and Hormonal Treatment
Biological: Tecemotide (L-BLP25) and Hormonal Treatment
Drug: cyclophosphamide
Drug: sodium chloride (NaCl)

Registration Number: NCT00925548

Lead Sponsor: EMD Serono

Brief 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).

Detailed Description: The purpose of the study is to determine whether the addition of the experimental mucinous glycoprotein 1 (MUC1) antigen-specific cancer immunotherapy tecemotide (L-BLP25) to hormonal treatment is effective in prolonging progression-free survival in postmenopausal women with endocrine-sensitive inoperable locally advanced, recurrent or metastatic breast cancer.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 16

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Investigational Arm	cyclophosphamide	Investigational Arm: * Pretreatment (Single Dose): 300 milligrams per square meter (mg/m\^2) up to a maximum dose of 600 mg of intravenous cyclophosphamide * tecemotide (L-BLP25) plus Hormonal Therapy (Standard Dose)
Control Arm	Placebo of tecemotide (L-BLP25) and Hormonal Treatment	Control Arm: * Pretreatment (Single Dose): sodium chloride (NaCl) 9 grams per liter (g/L) infusion * Placebo plus Hormonal Therapy (Standard Dose)
Investigational Arm	Tecemotide (L-BLP25) and Hormonal Treatment	Investigational Arm: * Pretreatment (Single Dose): 300 milligrams per square meter (mg/m\^2) up to a maximum dose of 600 mg of intravenous cyclophosphamide * tecemotide (L-BLP25) plus Hormonal Therapy (Standard Dose)
Control Arm	sodium chloride (NaCl)	Control Arm: * Pretreatment (Single Dose): sodium chloride (NaCl) 9 grams per liter (g/L) infusion * Placebo plus Hormonal Therapy (Standard Dose)

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	Time from randomization to disease progression, death or last tumor assessment, reported between day of first participant randomized i.e. 30 Sep 2009, until end of trial i.e. 27 Aug 2010	PFS was defined as the duration from randomization to first observation of progressive disease (PD) as confirmed by the independent radiological review or death.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS) Time	Time from randomization to death or last day known to be alive reported between day of first participant randomized i.e. 30 Sep 2009, until end of trial i.e. 27 Aug 2010	OS time was defined as the time from randomization to death. Participants without event were to be censored at the last date known to be alive or at the clinical cut-off date, whichever was earlier.
Percentage of Participants With Objective Tumor Response	Randomization until the date of first documented progression, until end of trial i.e. 27 Aug 2010	Percentage of participants with objective tumor response was to be reported. An objective response (OR) was defined as a participant having a best overall response of either confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST 1.0) as assessed by independent radiological review.
Duration of Response	Time from first assessment of CR or PR until PD, death or last tumor assessment, reported between day of first participant randomized i.e. 30 Sep 2009, until end of trial i.e. 27 Aug 2010	Duration of response is defined as the time from the first assessment of CR or PR until the date of the first occurrence of PD, or until the date of death.
Percentage of Participants With Clinical Benefit	Randomization until the date of first documented progression assessed up to end of trial i.e. 27 Aug 2010	Clinical Benefit is defined as having achieved at least disease stabilization; that is participants with confirmed CR, PR, or stable disease (SD,) lasting for at least 22 weeks.
Time to Progression (TTP)	Time from randomization to PD, reported between day of first participant randomized i.e. 30 Sep 2009, until end of trial i.e. 27 Aug 2010	TTP is defined as the time from date of randomization to the date of radiological diagnosis of PD (censoring for death without progression).
Time to Chemotherapy	Time from randomization to start of chemotherapy, reported between day of first participant randomized i.e. 30 Sep 2009, until end of trial i.e. 27 Aug 2010	Time to chemotherapy is defined as the time from date of randomization to the start date of chemotherapy.
Functional Assessment of Cancer Therapy-Breast (FACT-B) Questionnaire	Baseline, Week 9, 20, 32, 44 and end of trial visit	FACT-B questionnaire consists of 36 questions; 7 in physical well-being (PWB); 7 in social well-being (SWB); 6 in emotional well-being (EWB); 7 in functional well-being (FWB); 9 in breast cancer subscale (BCS). Trial outcome Index (TOI) was calculated by the sum of the physical well-being (PWB), functional well-being (FWB), and breast cancer scale (BCS) subscales of FACT-B. Total score of subscores or TOI is calculated from each score of question. Higher score means better and lower score means worthier. Score range; 0-28 in PWB; 0-28 in SWB; 0-24 in EWB; 0-28 in FWB; 0-36 in BCS; 0-92 in TOI.
European Questionnaire-5 Dimensions (EQ-5D) Questionnaire	Baseline, Week 9, 20, 32, 44 and end of trial visit	EQ-5D questionnaire is a measure of health status that provides a simple descriptive profile and a single index value. The optional part of the questionnaire was not applied. EQ-5D defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items are combined to generate health profiles. These profiles were to be converted to a continuous single index score using a one to one matching. The lowest possible score is -0.59 and the highest is 1.00. Higher scores on the EQ-5D represent a better quality of life (QoL) and lower scores on the EQ-5D represent a worst QoL.
Number of Participant Utilizing Healthcare Resources	Randomization up to end of trial visit	Healthcare Resource Utilization (HRU) parameters included direct medical resources (e.g., nonscheduled procedures, unplanned hospitalization, outpatient visits), nonmedical resources (e.g., travel, paid and unpaid assistance), and occupational resources (e.g., occupational changes and concerns).
Serum Carcinoma Antigen (CA) 15-3 Levels	Baseline, Week 5, 9, 20, 32, 44 and end of trial visit	CA 15-3 is a serum marker for breast cancer which is a possible measure for immune response.