Neoadjuvant treatment of WT1-positive Stage II or III breast cancer. Patients will receive the WT1-A10 + AS15 ASCI in combination with standard neodjuvant therapy. Patients will be recruited in different cohorts according to the standard neoadjuvant treatment they will receive (aromatase inhibitor, chemotherapy or chemotherapy combined with trastuzumab). MedDRA version: 14.1 Level: PT Classification code 10006200 Term: Breast cancer stage II System Organ Class: 10029104 - Neoplasms benign, mal
Conditions
Interventions
Product Name: WT1-A10 + AS15
Product Code: WT1-A10 + AS15
Pharmaceutical Form: Powder for solution for injection
Current Sponsor code: WT1-A10 protein
Concentration unit: µg microgram(s)
Concentration
Sponsors
GlaxoSmithKline Biologicals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The patient is at least 18 years of age at the time the informed consent to screening has been obtained. 2. The patient has proven T1 with lymph node involvement or T2-T4c, any N, M0 primary invasive breast cancer, histologically confirmed by core needle biopsy. Isolated supraclavicular lymph node involvement is allowed. 3. The patient’s tumor shows WT1 antigen expression, detected by quantitative RT-PCR or any updated technique at the time of sample analysis. 4. The patient has one of the following histologically confirmed breast cancer subtypes: •Estrogen receptor (ER) and/or progesterone (PgR) positive tumor •HER2-overexpressing breast cancer •HER2-negative breast cancer. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the time of study treatment allocation. 6. Baseline LVEF of equal or more than 50% as measured within six weeks prior to study treatment allocation by echocardiography or MUGA scan. 7. The patient shows normal organ function. 8. A female patient of childbearing potential may be enrolled in the study, if the patient: •has practiced adequate contraception for 30 days prior to study product administration, and •has a negative pregnancy test within one week prior to study treatment allocation, and •has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the study product administration series. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. The patient has inflammatory breast cancer, which is defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or peau d'orange without erythema). 2. Diagnosis established by incisional biopsy. 3. Prior and concomitant neoadjuvant anti-breast-cancer treatments such as chemotherapy, immunotherapy / biological response modifiers, endocrine therapy, and radiotherapy, unless authorized specifically by the protocol. 4. The patient is known to be human immunodeficiency virus (HIV)-positive. 5. The patient has symptomatic autoimmune disease such as, but not limited to multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded. 6. The patient is known to have difficult-to-control hypertension, coronary artery disease, arrhythmia requiring treatment, clinically significant valvular disease, cardiomegaly on chest X-ray, ventricular hypertrophy on ECG or previous myocardial infarction or congestive heart failure. 7. The patient has a history of allergic reactions likely to be exacerbated by any component of the investigational product used in the study. 8. The patient has other concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk. 9. The patient has (or has had) previous or concomitant malignancies at other sites, except effectively treated malignancy that is considered by the investigator highly likely to have been cured. 10. The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the study procedures. 11. The patient has received any investigational or non-registered product (e.g., drug or vaccine) within 30 days preceding the first dose of study products or planned use during the study period. 12. The patient requires concomitant treatment with any immunosuppressive agents or with systemic corticosteroids prescribed for chronic treatment (more than seven consecutive days). 13. The patient has a significant disorder of coagulation or receives treatment with warfarin derivatives or heparin. Patients receiving individual doses of low molecular wieght heparin outside of 24 hours prior to WT1-A10 + AS15 ASCI/placebo administration are eligible. Patients receiving prophylactic antiplatelet medications e.g. low-dose aspirin, and without a clinically apparent bleeding tendency are eligible.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Phase I segment Safety: Occurrence of severe toxicities i.e., 1. A Grade 3 or higher toxicity that is related or possibly related to the combined administration of standard treatment and WT1-A10 + AS15 ASCI/placebo. Grade 3 myalgia, athralgia, headache, fever, rigors/chills and fatigue (including lethargy, malaise and asthenia) should persist for 48 hours despite therapy in order to be considered as a severe toxicity. 2. A decrease in LVEF from baseline with 10 points or more and at <50% that is related or possibly related to the combined administration of standard treatment and WT1-A10 + AS15 ASCI/placebo and that is confirmed by a second LVEF assessment within approximately three weeks. 3. A Grade 2 (i.e., asymptomatic with testing that suggests ischemia; stable angina) or higher cardiac ischemia/infarction that is related or possibly related to the combined administration of standard treatment and WT1-A10 + AS15 ASCI/placebo. 4. A Grade 2 or higher allergic reaction occurring within 24 hours following the WT1-A10 + AS15 ASCI/placebo administration. 5. A Grade 3 or higher blood/bone marrow toxicity that is considered as related or possibly related to the combined administration of standard treatment and WT1-A10 + AS15 ASCI/placebo, i.e., •The hemoglobin level < 8.0 g/dL •The leukocyte count < 2.0 x 10E9/L •The neutrophil count < 1.0 x 10E9/L •The platelet count < 50.0 x 10E9/L Important note: Important note: In case of concomitant chemotherapy/trastuzumab (i.e., Cohort B, C, D or E) a Grade 3 or higher blood/bone marrow event will be considered as a severe toxicity only if it is NOT resolved to Grade <= 1 within five weeks post last chemotherapy administration. 6. A decrease in renal function at the time of WT1-A10 + AS15 ASCI/placebo administration that is considered as related or possibly related to the combined administration of standard treatment and WT1-A10 + AS15 ASCI/placebo and evaluated by a calculated creatinine clearance < | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): None;Timepoint(s) of evaluation of this end point: None | — |
Countries
Belgium, Denmark, France, Germany, Italy, Russian Federation, United Kingdom, United States
Contacts
Public ContactClinical Disclosure Advisor
GlaxoSmithKline Biologicals
Outcome results
None listed