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Vaccine Therapy With or Without Polysaccharide-K in Treating Patients With Stage IV HER2 Positive Breast Cancer Receiving HER2-Targeted Monoclonal Antibody Therapy

NCT01922921

Description:

This randomized phase I/II trial studies the side effects of vaccine therapy with or without polysaccharide-K and to see how well it works in treating patients with stage IV human epidermal growth factor receptor 2 (HER2) positive breast cancer who are receiving HER2-targeted monoclonal antibody therapy. Vaccines made from HER2 intracellular domain (ICD) peptide may help the body build an effective immune response to kill tumor cells that express HER2. Polysaccharide-K may stimulate the immune system in different ways and stop tumor cells from growing. It is not yet known whether vaccine therapy works better when given with or without polysaccharide-K in treating breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Vaccine Therapy With or Without Polysaccharide-K in Treating Patients With Stage IV HER2 Positive Breast Cancer Receiving HER2-Targeted Monoclonal Antibody Therapy
  • Official Title: Phase I/II Randomized Study of Combination Immunotherapy With or Without Polysaccharide Krestin (PSK®) Concurrently With a HER2 ICD Peptide-Based Vaccine in Patients With Stage IV Breast Cancer Receiving HER2-Targeted Monoclonal Antibody Therapy

Clinical Trial IDs

  • ORG STUDY ID: 7866
  • SECONDARY ID: NCI-2013-01377
  • SECONDARY ID: 135
  • SECONDARY ID: 7866/135
  • SECONDARY ID: 7866
  • SECONDARY ID: P30CA015704
  • SECONDARY ID: U19AT006028
  • NCT ID: NCT01922921

Conditions

  • HER2/Neu Positive
  • Recurrent Breast Carcinoma
  • Stage IV Breast Cancer

Interventions

DrugSynonymsArms
HER-2/neu Intracellular Domain ProteinHER-2 ICD Peptide, HER-2/neu ICD Protein, HER2 ICD, HER2 Intracellular DomainArm I (placebo)
Pertuzumab2C4, 2C4 Antibody, MoAb 2C4, Monoclonal Antibody 2C4, Perjeta, rhuMAb2C4, RO4368451Arm I (placebo)
Polysaccharide-KGlycoproteins, Krestin, KS-2, PSKArm II (polysaccharide-K)
TrastuzumabABP 980, Anti-c-ERB-2, Anti-c-erbB2 Monoclonal Antibody, Anti-ERB-2, Anti-erbB-2, Anti-erbB2 Monoclonal Antibody, Anti-HER2/c-erbB2 Monoclonal Antibody, Anti-p185-HER2, c-erb-2 Monoclonal Antibody, HER2 Monoclonal Antibody, Herceptin, Herceptin Biosimilar PF-05280014, Herceptin Trastuzumab Biosimilar PF-05280014, MoAb HER2, Monoclonal Antibody c-erb-2, Monoclonal Antibody HER2, PF-05280014, rhuMAb HER2, RO0452317, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar PF-05280014Arm I (placebo)

Purpose

This randomized phase I/II trial studies the side effects of vaccine therapy with or without polysaccharide-K and to see how well it works in treating patients with stage IV human epidermal growth factor receptor 2 (HER2) positive breast cancer who are receiving HER2-targeted monoclonal antibody therapy. Vaccines made from HER2 intracellular domain (ICD) peptide may help the body build an effective immune response to kill tumor cells that express HER2. Polysaccharide-K may stimulate the immune system in different ways and stop tumor cells from growing. It is not yet known whether vaccine therapy works better when given with or without polysaccharide-K in treating breast cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the safety of polysaccharide-K (PSK) when given with HER2-directed
      immunotherapy.

      SECONDARY OBJECTIVES:

      I. To evaluate the effect of PSK on natural killer (NK) cell functional activity when given
      with HER2-directed immunotherapy.

      TERTIARY OBJECTIVES:

      I. To investigate the effect of PSK when given with HER2-directed immunotherapy on: serum
      levels of pro-inflammatory cytokine and/or chemokines; intermolecular epitope spreading;
      serum transforming growth factor (TGF)-beta levels; progression free survival (PFS) and
      overall survival (OS).

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      ARM I: Patients receive HER2 ICD peptide-based vaccine intradermally (ID) once monthly for 3
      months, trastuzumab (or trastuzumab and pertuzumab) per standard of care, and placebo orally
      (PO) twice daily (BID) for 4 months.

      ARM II: Patients receive HER2 ICD peptide-based vaccine ID and trastuzumab (or trastuzumab
      and pertuzumab) as in Arm I and polysaccharide-K PO BID for 4 months.

      After completion of study treatment, patients are followed up for 9 months and then twice
      annually for 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (placebo)Active ComparatorPatients receive HER2 ICD peptide-based vaccine ID once monthly for 3 months, trastuzumab (or trastuzumab and pertuzumab) per standard of care, and placebo PO BID for 4 months.
    Arm II (polysaccharide-K)ExperimentalPatients receive HER2 ICD peptide-based vaccine ID and trastuzumab (or trastuzumab and pertuzumab) as in Arm I and polysaccharide-K PO BID for 4 months.

      Eligibility Criteria

              Inclusion Criteria:
      
                -  Patients with stage IV HER2+ breast cancer treated to:
      
                     -  No evidence of disease (NED), or
      
                     -  Stable bone only disease after definitive therapy
      
                -  HER2 overexpression by immunohistochemistry (IHC) of 2+ or 3+ in the primary tumor or
                   metastasis; or documented gene amplification by fluorescent in situ hybridization
                   (FISH) analysis; IHC =< 2+ must have HER2 gene amplification documented by FISH
      
                -  Patients must continue HER2-targeted monoclonal antibody therapy dosing per standard
                   of care through the entire study period (one year)
      
                     -  HER2-targeted monoclonal antibody therapy is defined as either trastuzumab
                        monotherapy, or trastuzumab and pertuzumab combination therapy administered per
                        standard of care
      
                -  Patients must be at least 21 days post cytotoxic chemotherapy prior to enrollment
      
                -  Patients must be at least 28 days post immunosuppressants prior to enrollment
      
                -  Patients must be at least 28 days from use of any mushroom supplements (examples:
                   turkey tail, reishi, maitake, shiitake) and agree to withhold them for the entire
                   study period (one year)
      
                -  Patients on bisphosphonates and/or endocrine therapy are eligible
      
                -  Patients who are having sex that could lead to pregnancy must agree to contraceptive
                   use during the entire study period
      
                -  Patients must have Zubrod performance status score of =< 2
      
                -  Patients must have recovered from major infections and/or surgical procedures, and in
                   the opinion of the investigator, not have significant active concurrent medical
                   illnesses precluding study treatment
      
                -  White blood cell (WBC) >= 3000/mm^3
      
                -  Hemoglobin (Hgb) >= 10 g/dl
      
                -  Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min
      
                -  Total bilirubin =< 1.5 mg/dl
      
                -  Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 times the upper limit of normal
      
                -  Patients must have adequate cardiac function as demonstrated by normal left
                   ventricular ejection fraction (LVEF) >= the lower limit of normal for the facility on
                   multi gated acquisition (MUGA) scan or echocardiogram (ECHO) within 3 months of
                   enrollment
      
              Exclusion Criteria:
      
                -  Patients with any of the following cardiac conditions:
      
                     -  Restrictive cardiomyopathy
      
                     -  Unstable angina within 6 months prior to enrollment
      
                     -  New York Heart Association functional class III-IV heart failure
      
                     -  Symptomatic pericardial effusion
      
                -  Patients with any contraindication to receiving rhu granulocyte macrophage colony
                   stimulating factor (rhuGM-CSF) based products
      
                -  Patients with any clinically significant autoimmune disease requiring active treatment
      
                -  Patients receiving any concurrent immunosuppressants
      
                -  Patients who are pregnant or breast-feeding
      
                -  Patients who are simultaneously enrolled in other treatment studies
      
                -  Patients who have received a previous HER2 breast cancer vaccine
      
                -  Known hypersensitivity reaction to mushroom products
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Incidence of grade 3 or higher toxicity (including systemic and local injection site reactions) graded per Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events 4.0
      Time Frame:Up to 4 months
      Safety Issue:
      Description:Evaluated using physical examination and clinical labs. Type and grade of toxicities noted during treatment will be summarized.

      Secondary Outcome Measures

      Measure:Induction of interferon (IFN)-gamma production and cluster of differentiation (CD)107a expression in NK cells, via flow cytometry
      Time Frame:Up to 16 weeks
      Safety Issue:
      Description:Augmentation of NK cell activity is defined by a 2-fold increase in NK cell IFN-gamma production and CD107a expression from baseline after 4 weeks of oral administration of polysaccharide-K.

      Details

      Phase:Phase 1/Phase 2
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:University of Washington

      Last Updated

      January 18, 2017