Clinical Trial 18079

Cancer Type: Breast
Interventions:E75; GM-CSF; Herceptin (Trastuzumab); Leukine (GM-CSF); Placebo; sargramostatin (GM-CSF)

Study Type: Treatment
Phase of Study: Phase II

  • Hatem Soliman


Study Title

Combination Immunotherapy with Herceptin and the HER2 Vaccine E75 in Low and Intermediate HER2-expressing Breast Cancer Patients to Prevent Recurrence


The purpose of this study is to (1) test the HER2/neu peptide (piece of the protein) E75 as a vaccine in combination with Herceptin (trastuzumab) to determine if it can prevent breast cancer recurrence; (2) to look at the immune system's response to the vaccine in combination with Herceptin; (3) to collect information on the vaccine in combination with Herceptin's safety and dosing.


In this study, we intend to assess the ability of the combination of Herceptin and the HER2 vaccine E75 (administered with the immunoadjuvant GM-CSF) given in the adjuvant setting to prevent recurrences in NP (or NN if negative for both estrogen (ER) and progesterone (PR) receptors) breast cancer patients with tumors that express low (1+) or intermediate (2+) levels of HER2. Enrolled patients will be randomized to receive Herceptin and E75 + GM-CSF or Herceptin with GM-CSF alone (no E75). The safety of the combination therapy will be documented, specifically to ensure that no additive cardiac toxicity results from combination HER2-directed therapy. Efficacy will be documented by comparing the DFS and immunological responses between treatment groups. Primary Objectives: The primary efficacy endpoint is to compare DFS at 24 months between treatment groups. The primary safety issue is to prove there is no additive cardiac toxicity with combination HER2-directed therapy. Secondary Objectives: A secondary endpoint of the trial is to compare DFS at 36 months. Immunologic responses to the vaccine will also be documented and correlated to clinical benefit.

Inclusion Criteria


  • Women 18 years or older.
  • Node-positive breast cancer (AJCC N1, N2, or N3).
  • Node-negative breast cancer if negative for both estrogen (ER) and progesterone (PR) receptors and have received chemotherapy as standard of care.
  • Clinically cancer-free (no evidence of disease) after standard of care therapy (surgery, chemotherapy, radiation therapy as directed by NCCN guidelines). Hormonal therapy will continue per standard of care. Neoadjuvant chemotherapy is allowed.
  • Recovery from any toxicity(ies) associated with prior adjuvant therapy.
  • HER2 expression of 1+ or 2+ by IHC. FISH testing must be performed on IHC 2+ tumors and shown to be non-amplified (≤2.2).
  • HLA-A2, A3, A24, or A26 positive.
  • LVEF >50%, or an LVEF within the normal limits of the institution's specific testing (MUGA or Echo).
  • Eastern Cooperative Oncology Group (ECOG) performance status 0,1.
  • Signed informed consent.
  • Adequate birth control (abstinence, hysterectomy, bilateral oophorectomy, bilateral tubal ligation, oral contraception, IUD, or use of condoms or diaphragms).
  • Must start study treatment (receive first Herceptin infusion) between 3-12 weeks from completion of standard of care therapy.

  • Exclusion Criteria


  • Node-negative breast cancer (AJCC N0 or N0(i+)) unless negative for both estrogen (ER) and progesterone (PR) receptors and has received chemotherapy as standard of care.
  • Clinical or radiographic evidence of distant or residual breast cancer.
  • HER2 negative (IHC 0) or HER2 3+ or FISH amplified (FISH >2.2).
  • Non-HLA-A2/3/24/or A26 positivity.
  • History of prior Herceptin therapy.
  • NYHA stage 3 or 4 cardiac disease.
  • LVEF > Immune deficiency disease or HIV, HBV, HCV.
  • Receiving immunosuppressive therapy including chemotherapy, chronic steroids, methotrexate, or other known immunosuppressive agents.
  • ECOG ≥2.
  • Tbili >1.8, creatinine>2, hemoglobin> Pregnancy (assessed by urine HCG).
  • Breast feeding.
  • History of autoimmune disease.
  • Active pulmonary disease requiring medication to include multiple inhalers.
  • Involved in other experimental protocols (except with permission of the other study Principal Investigator).