Combination immunotherapy with Herceptin and the HER2 vaccine E75 in low and intermediate HER2- expressing breast cancer patients to prevent recurrence
You are being asked to take part in this study because you have been treated for node-positive (NP) or high-risk node-negative (NN) breast cancer, you are at risk for recurrence (your breast cancer coming back), and your tumor cells show a specific protein called HER2/neu on their cell surfaces. The goal of this clinical research study is to learn if the HER2/neu vaccine E75, when given in combination with GM-CSF and Herceptin (trastuzumab), may help prevent breast cancer from coming back. The safety of this drug combination will also be studied.
Disease Group: Breast
Treatment Agent: Herceptin,NeuVax
Treatment Location: Both at MDACC & and Other Sites
Sponsor: Cancer Insight, LLC,Galena Biopharma,Genentech, Inc.
PRIMARY OBJECTIVES The primary efficacy endpoint is to compare disease-free survival (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.
IRB Review and Approval Date: 09/11/2013
Recruitment Status: Open
Projected Accrual: 300
1) Women 18 years or older.
2) Node-positive breast cancer (American Joint Committee on Cancer [AJCC] N1, N2, or N3).
3) Node-negative breast cancer if negative for both estrogen (ER) and progesterone (PR) receptors and have received chemotherapy as standard of care.
4) Clinically cancer-free (no evidence of disease) after standard of care therapy (surgery, chemotherapy, radiation therapy as directed by National Comprehensive Cancer Network (NCCN) guidelines). Hormonal therapy will continue per standard of care. Neoadjuvant chemotherapy is allowed.
5) Recovery from any toxicity(ies) associated with prior adjuvant therapy.
6) HER2 expression of 1+ or 2+ by immunohistochemistry (IHC). Fluorescence in situ hybridization (FISH) or Dual-ish testing must be performed on IHC 2+ tumors and shown to be non-amplified by FISH (</= 2.0) or by Dual-ish (</=2.0).
7) Human leukocyte antigen (HLA)-A2 and/or HLA-A3 and/or HLA-A24 and/or HLA-A26 positive.
8) Left ventricular ejection fraction (LVEF) >/= 50%, or an LVEF within the normal limits of the institution’s specific testing (MUGA or Echocardiogram) (ECHO).
9) Eastern Cooperative Oncology Group (ECOG) 0,1.
10) Signed informed consent.
11) Adequate birth control (abstinence, hysterectomy, bilateral oophorectomy, bilateral tubal ligation, oral contraception, IUD, or use of condoms or diaphragms).
12) Must start study treatment (receive first Herceptin infusion) between 3-12 weeks from completion of standard of care therapy.
1) 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.
2) Clinical or radiographic evidence of distant or residual breast cancer.
3) HER2 negative (IHC 0) or HER2 3+ or FISH/Dual-ish amplified (FISH >2.0; Dual-ish >2.0).
4) HLA-A2, A3, A24 and A26 negative.
5) History of prior Herceptin (trastuzumab) therapy.
6) NYHA stage 3 or 4 cardiac disease.
7) LVEF <50%, or less than the normal limits of the institution’s specific testing (MUGA or ECHO).
8) Immune deficiency disease or HIV, HBV, HCV.
9) Receiving immunosuppressive therapy including chemotherapy, chronic steroids, methotrexate, or other known immunosuppressive agents.
10) ECOG >/= 2.
11) Tbili >1.8, creatinine>2, hemoglobin<10, platelets<50,000, WBC<2,000.
12) Pregnancy (assessed by urine HCG).
13) Breast feeding.
14) Any active autoimmune disease, requiring treatment with the exception of vitiligo.
15) Active pulmonary disease requiring medication to include multiple inhalers.
16) Involved in other experimental protocols (except with permission of the other study PI).