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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HER2/Neu Positive
- Sponsor
- University of Washington
- Enrollment
- 31
- Locations
- 1
- Primary Endpoint
- Number of Patients With Grade 3 or Higher Toxicity Per Study Arm.
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Investigators
William Rayford Gwin III, MD
Assistant Professor
University of Washington
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
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
Outcomes
Primary Outcomes
Number of Patients With Grade 3 or Higher Toxicity Per Study Arm.
Time Frame: Up to 4 months
Evaluated using physical examinations and clinical labs by type and grade of toxicities noted during treatment, There were graded per Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events 4.0.
Secondary Outcomes
- Induction of Interferon (IFN)-Gamma Production and Cluster of Differentiation (CD)107a Expression in NK Cells, Via Flow Cytometry(Up to 16 weeks)