Combination Immunotherapy With Herceptin and the HER2 Vaccine NeuVax
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Herceptin; NeuVax vaccine; GM-CSF
Intervention description: Herceptin will be administered to patients every three weeks as monotherapy for one year, to be given upon completion of standard of care chemotherapy/radiotherapy. The first Herceptin infusion will be given no sooner than three weeks and no later than 12 weeks after completion of chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk.; At the time of vaccine administration, a frozen solution of E75 acetate (1.5mg/ml) is thawed and 1000mcg E75 peptide mixed thoroughly with 250mcg GM-CSF. This constitutes the NeuVax vaccine. For patients randomized to the Herceptin + NeuVax vaccine arm, they will commence Herceptin monotherapy and then will begin the NeuVax vaccine series immediately after completion of the third Herceptin infusion. The vaccine series consists of NeuVax vaccine administered intradermally every three weeks for six total vaccinations, 30-120 minutes after completion of Herceptin infusion.; For patients randomized to the Herceptin + GM-CSF only arm, they will commence Herceptin monotherapy and then will begin the GM-CSF inoculation series immediately after completion of the third Herceptin infusion. The GM-CSF inoculation series consists of 250mcg GM-CSF administered intradermally every three weeks for six total vaccinations, 30-120 minutes after completion of Herceptin infusion.
Intervention MeSH terms: Trastuzumab; Molgramostim; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 275.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; male breast cancer

Summary:

      The study will be a multi-center, prospective, randomized, single-blinded, placebo-controlled
      Phase II trial of Herceptin + NeuVax(TM) vaccine (E75 peptide/granulocyte macrophage-colony
      stimulating factor) (GM-CSF) versus Herceptin + GM-CSF alone. The target study population is
      node-positive (NP) (or node-negative [NN] if negative for both ER and PR) breast cancer
      patients with HER2 1+ and 2+ expressing tumors who are disease-free after standard of care
      therapy. Disease-free subjects after standard of care multi-modality therapy will be screened
      and HLA-typed. E75 is a CD8-eliciting peptide vaccine that was restricted to HLA-A2+ or
      HLA-A3+ patients (approximately two-thirds of the US population), and has been extended to
      HLA-A24+ and HLA-A26+ as well.
    

Eligibility criteria:

        Patients will be included in the study based on the following 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 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).

          -  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)

          -  ECOG 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) 15between 3-12 weeks
             from completion of standard of care therapy.

        4.1.3 Exclusion Criteria

        Patients will be excluded from the study based on the following 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 FISHDual-ISH amplified (FISH >2.0); Dual-ISH >2.0

          -  HLA-A2, A3, A24, A26 negative

          -  History of prior Herceptin therapy

          -  NYHA stage 3 or 4 cardiac disease

          -  LVEF <50%, or less than the normal limits of the institution's specific testing (MUGA
             or Echo)

          -  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<10, platelets<50,000, WBC<2,000

          -  Pregnancy (assessed by urine HCG)

          -  Breast feeding

          -  Any active autoimmune disease requiring treatment, with the exception of vitiligo

          -  Active pulmonary disease requiring medication to include multiple inhalers

          -  Involved in other experimental protocols (except with permission of the other study
             PI)