Evaluation of an Anti-cancer Immunotherapy Combined With Standard Neoadjuvant Treatment in Patients With WT1-positive Primary Invasive Breast Cancer
Condition: Neoplasms, Breast
MeSH terms: Breast Neoplasms
Intervention: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A; Placebo; Aromatase inhibitor; 5-Fluorouracil; Carboplatin AUC; Cyclophosphamide; Docetaxel; Doxorubicin; Epirubicin; Paclitaxel; Trastuzumab
Intervention description: 6 or 8 injections at 3 weeks apart, injected intramuscularly in the deltoid or lateral region of the thigh.; 6 or 8 doses at 3 weeks apart of sucrose/mannitol-based formulation reconstituted with an oil-in-water emulsion, injected intramuscularly in the deltoid or lateral region of the thigh.; This treatment consisted of any aromatase inhibitor (e.g. letrozole or exemestane), administered intravenously in Cohort A Groups daily for either 18 (if 6 doses of WT1 ASCI/placebo) or 24 weeks (if 8 doses of WT1 ASCI/placebo).; Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses at 3 weeks apart, and for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.; Administered intravenously in Cohort C Groups in 6 doses at 3 weeks apart, on the same day as WT1 ASCI/placebo administration (Day 1 of each cycle).; Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses in Cohort C Groups and 6 doses 3 weeks apart in Cohorts A Placebo, B and D Groups, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.; Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.; Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 6 doses 3 weeks apart (Cohort C patients with this schedule did not receive this treatment), while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.; Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.; Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: only in the 8 WT1 ASCI-dose schedule patients received 4 at 3 weeks apart or 12 weekly doses. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.; Administered intravenously in Cohort C Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohort B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.
Intervention MeSH terms: Paclitaxel; Docetaxel; Cyclophosphamide; Carboplatin; Doxorubicin; Fluorouracil; Trastuzumab; Epirubicin; Aromatase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 66.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: WT1; neoadjuvant; tumor antigen; immunotherapy; breast cancer; adult

Summary:

      The purpose of this study is to evaluate the safety, immunogenicity and clinical activity of
      a new WT1 anti-cancer immunotherapy in patients with WT1-positive Stage II or III breast
      cancer. The treatment will be given before surgery in combination with standard therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The patient is ≥ 18 years of age at the time the informed consent to screening has
             been obtained.

          -  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.

          -  The patient's tumor shows WT1 antigen expression.

          -  The patient has one of the following histologically confirmed breast cancer subtypes:

               -  Estrogen receptor and/or progesterone positive tumor.

               -  Human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer.

               -  HER2-negative breast cancer.

          -  Eastern Cooperative Oncology Group (performance status of 0 or 1 at the time of study
             treatment allocation.

          -  Baseline left ventricular ejection fraction of ≥ 50% as measured within six weeks
             prior to study treatment allocation by echocardiography or multi-gated
             acquisition(MUGA)scan.

          -  The patient shows normal organ function according to the following parameters(as
             measured within six weeks prior to treatment allocation)::

               -  Hemoglobin: Within normal range according to institutional standards.

               -  Absolute leukocyte count: Within normal range according to institutional
                  standards.

               -  Absolute lymphocyte count: Within normal range according to institutional
                  standards.

               -  Platelet count: Within normal range according to institutional standards

               -  Alanine aminotransferase: ≤ 2.5 x Upper Limit of Normal (ULN)

               -  Aspartate aminotransferase: ≤ 2.5 x ULN

               -  Total bilirubin: ≤ 1.5 x ULN. In the case of known Gilbert's syndrome ≤ 2 x ULN

               -  Serum creatinine: 1.5 x ULN

               -  Calculated creatinine clearance: > 50 mL/min

          -  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 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.In
                  view of the investigator, the patient can and will comply with the requirements
                  of the protocol.

          -  Written informed consent has been obtained from the patient prior to performance of
             any study specific procedure.

        Exclusion Criteria:

          -  The patient has inflammatory breast cancer, which is defined as clinically significant
             erythema of the breast and/or documented dermal lymphatic invasion.

          -  Diagnosis established by incisional biopsy.

          -  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.

          -  The patient is known to be human immunodeficiency virus -positive.

          -  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.

          -  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 electrocardiogram or previous
             myocardial infarction or congestive heart failure.

          -  The patient has a history of allergic reactions likely to be exacerbated by any
             component of the investigational product used in the study.

          -  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.

          -  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.

          -  The patient has psychiatric or addictive disorders that may compromise his/her ability
             to give informed consent or to comply with the study procedures.

          -  The patient has received any investigational or non-registered product within 30 days
             preceding the first dose of study products or planned use during the study period.

          -  The patient requires concomitant treatment with any immunosuppressive agents or with
             systemic corticosteroids prescribed for chronic treatment.

          -  The patient has a significant disorder of coagulation or receives treatment with
             warfarin derivatives or heparin. Patients receiving individual doses of low molecular
             weight 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.