Clinical trial NCT00925548: STRIDE - STimulating Immune Response In aDvanced brEast Cancer
Official title: 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 Locally Advanced, Recurrent, or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Breast Cancer
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
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
First posted: 2009-06-22
Enrollment: 16
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 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
Secondary outcomes:
measure: Overall Survival (OS) Time
timeFrame: 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
measure: Percentage of Participants With Objective Tumor Response
timeFrame: Randomization until the date of first documented progression, until end of trial i.e. 27 Aug 2010
measure: Duration of Response
timeFrame: 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
measure: Percentage of Participants With Clinical Benefit
timeFrame: Randomization until the date of first documented progression assessed up to end of trial i.e. 27 Aug 2010
measure: Time to Progression (TTP)
timeFrame: 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
measure: Time to Chemotherapy
timeFrame: 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
measure: Functional Assessment of Cancer Therapy-Breast (FACT-B) Questionnaire
timeFrame: Baseline, Week 9, 20, 32, 44 and end of trial visit
measure: European Questionnaire-5 Dimensions (EQ-5D) Questionnaire
timeFrame: Baseline, Week 9, 20, 32, 44 and end of trial visit
measure: Number of Participant Utilizing Healthcare Resources
timeFrame: Randomization up to end of trial visit
measure: Serum Carcinoma Antigen (CA) 15-3 Levels
timeFrame: Baseline, Week 5, 9, 20, 32, 44 and end of trial visit
Other outcomes:
Locations:
city: Hickory
country: United States
facility: Research Site
state: North Carolina
city: Bedford Park, SA
country: Australia
facility: Research Site
city: Innsbruck
country: Austria
facility: Research Site
city: Salzburg
country: Austria
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Pardubice
country: Czech Republic
facility: Research Site
city: Praha
country: Czech Republic
facility: Research Site
city: Chemnitz
country: Germany
facility: Research Site
city: Darmstadt
country: Germany
facility: Research Site
city: Frankfurt am Main
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Kiel
country: Germany
facility: Research Site
city: Lübeck
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Rostock
country: Germany
facility: Research Site
city: Tübingen
country: Germany
facility: Research Site
city: Wiesbaden
country: Germany
facility: Research Site
city: Beer Yaakov
country: Israel
facility: Research Site
city: Gyeonggi-do
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Opole
country: Poland
facility: Research Site
city: Obninsk
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Tula
country: Russian Federation
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Nitra
country: Slovakia
facility: Research Site
city: Poprad
country: Slovakia
facility: Research Site
city: Trnava
country: Slovakia
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
Study officials:
affiliation: EMD Serono
name: Oscar Kashala, MD, PhD, DSc
role: STUDY_DIRECTOR
References: