ABCSG 34 Details

A prospective, open, randomized, phase-II-study of a therapeutic cancer vaccine (L-BLP25, Tecemotide) in the pre-operative treatment of women with primary breast cancer

Start:
01/2012

Contact ABCSG-Trial office

E-mail: info@abcsg.at
Phone: +43 1 408 92 30
Fax: +43 1 409 09 90

Design

ABCSG-34-Design
Click to enlarge

Primary objectives:

  • To compare efficacy of pre-operative standard of care treatment with or without a therapeutic cancer vaccine (L-BLP25), measured

Secondary objectives:

  • To compare the efficacy of pre-operative standard of care treatment with or without a therapeutic cancer vaccine (L-BLP25), when measured by pathological complete response (pCR = absence of invasive cancer cells in surgical specimen) at the time of surgery.
  • To detect differences in the efficacy between reverse versus conventional sequenced chemotherapy with or without L-BLP25, when measured by RCB.
  • To compare safety and tolerability of standard of care pre-operative treatment with or without a therapeutic cancer vaccine (L-BLP25).
  • To compare differences in tumor associated lymphocytes and ki67 tumor status along the course of therapy in women who receive standard of care pre-operative treatment with or without L-BLP25
  • To evaluate Quality of Life in women treated with our without a therapeutic cancer vaccine (L-BLP25)
  • Additional sensitivity analyses of pre-defined subgroups

Inclusion criteria:

  1. Pre- and postmenopausal female patients with core-biopsied, early primary invasive breast cancer of any clinical and/or radiological tumor stage (except T4d, inflammatory breast cancer) scheduled to receive pre-operative therapy
  2. One core from the biopsy will be dedicated to analyses of a validated gene expression array
  3. Patients must fulfill the following criteria:

    Postmenopausal AND E+++ or [E++ and ki67<14%] AND G 1,2,X AND scheduled for endocrine therapy as standard of care (34 A)

    OR

    Triple negative OR E- OR E+ OR [E++ and ki67≥14%] OR G3 OR premenopausal status AND scheduled for anthracyclin-taxan-based chemotherapy as institutional standard of care (34 B)

    Note: for ki67 status determination any antibody can be used [83]; scores for determination of ER/PR receptor status according to institutional standard

  4. No distant metastasis (M0) or secondary carcinoma as assessed clinically and radiologically (X-Ray or CT or MRI or PET) within 3 months prior randomization
  5. Age ≥ 18
  6. WHO performance status 0 or 1
  7. No prior chemotherapy, radiotherapy, or endocrine therapy for invasive breast cancer
  8. Willingness to undergo Sln and/or ALND Procedure (Sentinel/Axillary Lymph node dissection) according to institutional standard
  9. No medical and/or cardiologic contraindication to receive an anthracyclin- and taxan-containing chemotherapy or endocrine therapy regimen
  10. Adequate Hematologic function, as follows (≤ 14 days prior to randomization):
    • absolute neutrophil count (ANC) > 1.5 x 109/L
    • leucocyte count > 3.0 x 109/L
    • platelet count > 140 x 109/L
    • hemoglobin > 9 x g/dL
  11. Adequate Renal function, as follows (≤ 14 days of randomization):
    creatinin ≤ 1.5 x upper limit of normal (ULN)
  12. Adequate Hepatic function, as follows (≤ 14 days of randomization):
    • aspartate aminotransferase (ASAT) ≤ 2,5 x ULN
    • alanine aminotransferase (ALAT) ≤ 2,5 x ULN
    • total bilirubin ≤ 1.5 x ULN
  13. Adequate cardiac function: Normal cardiac function must be confirmed by LVEF (Echocardiography or MUGA scan) for chemotherapy treatment only. The result must be above 50% or above the lower normal limit of the institution. In addition each of the following criteria must be met:
    • NYHA<III
    • No uncontrolled angina, arrhythmia, hypertension
    • No myocardial infarction
  14. Negative pregnancy test (serum or urine) max. 7 days prior to randomization for pre-menopausal patients. In postmenopausal patients, no pregnancy tests must be performed at any time, requested that a) FSH and estradiol are in postmenopausal range and/or b) the patient is amenorrhoeic for > 12 months with uterus still in situ and/or c) the patient is 61 years of age or older. In this situation, the investigator must document why the pregnancy test was not performed
  15. In all premenopausal patients adequate contraception with non-hormonal methods (e.g. condoms, non-levonorgestrel-releasing intrauterine devices, diaphragms, vasectomized partner, or abstinence) is mandatory during study duration until at least 30 days after the last vaccination of L-BLP25
  16. Competent to comprehend, sign, and date an IEC/IRB-approved informed consent form and able to comply with the required treatments, visits and assessments
  17. Informed consent signed prior to randomization and prior to any study

Exclusion criteria:

  1. HER2 overexpression (+++)
  2. Past or current history of other malignant neoplasms in the last 5 years, except basal cell cancer of the skin, non-melanoma skin cancer and in situ cancer of the cervix
  3. Any medical condition rendering the patient unfit for standard of care pre-operative therapy (chemotherapy or endocrine therapy in the respective SoC treatment group)
  4. Concurrent or prior systemic antitumor therapy < 5 years
  5. Patients scheduled for any chemotherapy other than ECT or TEC
  6. Clinically significant cardiovascular disease (including unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) < 1 year before randomization
  7. Known autoimmune disease (e.g. rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, Crohn´s disease, multiple sclerosis, ankylosing spondylitis)
  8. Severely compromised haematopoietic function
  9. Known immunodeficiency disease (cellular immunodeficiency, hypogammaglobulinaemia, dysgamaglobulinaemia)
  10. Known positive test(s) for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic active hepatitis B infection
  11. Active infection requiring systemic treatment or any uncontrolled infections < 14 days prior to randomization
  12. Major surgery, or significant traumatic injury occurring within 4 weeks prior randomization
  13. Use of i.v. or s.c. immune modulators (Viscum album etc.)
  14. Pre-treatment with L-BLP25
  15. Concurrent treatment with another approved or investigational anticancer treatment is not permitted, excluding therapy as permitted in the protocol
  16. Concurrent participation in another clinical trial with the same endpoints is not permitted
  17. Pregnancy or breastfeeding
  18. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or IMP/NIMP administration, or which, in the judgment of the investigator, would make the patient inappropriate for enrollment into this study
  19. Known hypersensitivity against taxanes and/or epirubicin and/or cyclophosphamide or aromatase inhibitors in the respective SoC treatment group
  20. Concurrent treatment with corticosteroids except as use for the prophylactic medication regimen, inhalational use, prevention or treatment of acute hypersensitivity reactions, treatment of nausea / vomiting or chronic treatment (initiated > 6 months prior to study entry) at low dose (< 20 mg methylprednisolone or equivalent)