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STRIDE - STimulating Immune Response In aDvanced brEast Cancer

This study has been terminated.
(See termination reason in the below Purpose statement)
Sponsor:
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT00925548
First received: June 17, 2009
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

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).


Condition Intervention Phase
Breast Cancer
Biological: Tecemotide (L-BLP25) and Hormonal Treatment
Biological: Placebo of tecemotide (L-BLP25) and Hormonal Treatment
Drug: cyclophosphamide
Drug: sodium chloride (NaCl)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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:
  • Overall Survival (OS) Time [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Randomization until the date of first documented progression, until end of trial i.e. 27 Aug 2010 ] [ Designated as safety issue: No ]
    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 Frame: 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Randomization until the date of first documented progression assessed up to end of trial i.e. 27 Aug 2010 ] [ Designated as safety issue: No ]
    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 Frame: 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 ] [ Designated as safety issue: No ]
    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 Frame: 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 9, 20, 32, 44 and end of trial visit ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 9, 20, 32, 44 and end of trial visit ] [ Designated as safety issue: No ]
    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 [ Time Frame: Randomization up to end of trial visit ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 5, 9, 20, 32, 44 and end of trial visit ] [ Designated as safety issue: No ]
    CA 15-3 is a serum marker for breast cancer which is a possible measure for immune response.


Enrollment: 16
Study Start Date: September 2009
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Investigational Arm

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)
Biological: Tecemotide (L-BLP25) and Hormonal Treatment

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)

Drug: cyclophosphamide
300 mg/m^2 (to a maximum of 600 mg) of intravenous cyclophosphamide.
Active Comparator: Control Arm

Control Arm:

  • Pretreatment (Single Dose): sodium chloride (NaCl) 9 grams per liter (g/L) infusion
  • Placebo plus Hormonal Therapy (Standard Dose)
Biological: Placebo of tecemotide (L-BLP25) and Hormonal Treatment

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).

Drug: sodium chloride (NaCl)
NaCl 9 g/L infusion

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00925548

  Hide Study Locations
Locations
United States, North Carolina
Research Site
Hickory, North Carolina, United States
Australia
Research Site
Bedford Park, SA, Australia
Austria
Research Site
Innsbruck, Austria
Research Site
Salzburg, Austria
Belgium
Research Site
Leuven, Belgium
Czech Republic
Research Site
Pardubice, Czech Republic
Research Site
Praha, Czech Republic
Germany
Research Site
Chemnitz, Germany
Research Site
Darmstadt, Germany
Research Site
Frankfurt am Main, Germany
Research Site
Hamburg, Germany
Research Site
Kiel, Germany
Research Site
Lübeck, Germany
Research Site
München, Germany
Research Site
Rostock, Germany
Research Site
Tübingen, Germany
Research Site
Wiesbaden, Germany
Israel
Research Site
Beer Yaakov, Israel
Korea, Republic of
Research Site
Gyeonggi-do, Korea, Republic of
Research Site
Seoul, Korea, Republic of
Poland
Research Site
Opole, Poland
Russian Federation
Research Site
Obninsk, Russian Federation
Research Site
Saint-Petersburg, Russian Federation
Research Site
Tula, Russian Federation
Slovakia
Research Site
Bratislava, Slovakia
Research Site
Nitra, Slovakia
Research Site
Poprad, Slovakia
Research Site
Trnava, Slovakia
South Africa
Research Site
Johannesburg, South Africa
Sponsors and Collaborators
EMD Serono
Investigators
Study Director: Oscar Kashala, MD, PhD, DSc EMD Serono
  More Information

No publications provided

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00925548     History of Changes
Other Study ID Numbers: EMR 200038-010, 2008-005544-17
Study First Received: June 17, 2009
Results First Received: June 24, 2014
Last Updated: July 23, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: Ministry of Health
Canada: Health Canada
China: Food and Drug Administration
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
India: Ministry of Health
Ireland: Irish Medicines Board
Israel: Ministry of Health
Italy: The Italian Medicines Agency
Mexico: Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Norway: Norwegian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Authority of Medicines and Health Products (INFARMED, I.P.)
Russia: Ministry of Health of the Russian Federation
Slovakia: State Institute for Drug Control
South Africa: Department of Health
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
Taiwan: Department of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by EMD Serono:
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

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Cyclophosphamide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014