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Vaccine Therapy and Trastuzumab With or Without Polysaccharide-K in Treating Patients With Stage IV HER2 Positive Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Washington
Sponsor:
Collaborators:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT01922921
First received: August 1, 2013
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

This randomized phase I/II trial studies the side effects of vaccine therapy and trastuzumab 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. Vaccines made from HER2 intracellular domain (ICD) peptide may help the body build an effective immune response to kill tumor cells that express HER2. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumors to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Polysaccharide-K may stimulate the immune system in different ways and stop tumor cells from growing. It is not yet known whether vaccine therapy and trastuzumab is more effective when given with or without polysaccharide-K in treating breast cancer.


Condition Intervention Phase
HER2-positive Breast Cancer
Male Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Biological: HER-2/neu intracellular domain protein
Biological: trastuzumab
Other: placebo
Biological: polysaccharide-K
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Phase I/II Randomized Study of Combination Immunotherapy With or Without Polysaccharide Krestin (PSK®) Concurrently With a HER2 ICD Peptide-Based Vaccine and Trastuzumab in Patients With Stage IV Breast Cancer

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Incidence of grade 3 or higher toxicity (including systemic and local injection site reactions) graded per Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) 4.0 [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]
    Evaluated using physical examination and clinical labs. Type and grade of toxicities noted during treatment will be summarized.


Secondary Outcome Measures:
  • Induction of IFN-gamma production and CD107a expression in NK cells, via flow cytometry [ Time Frame: Up to 16 weeks ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Change in pro-inflammatory serum cytokine and/or chemokines assessed by Luminex analysis [ Time Frame: Baseline to 24 hours after completion of treatment ] [ Designated as safety issue: No ]
  • Change in intermolecular epitope spreading assessed by interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) assay [ Time Frame: Baseline to 12 months after completion of treatment ] [ Designated as safety issue: No ]
  • Change in serum TGF-beta levels assessed by enzyme-linked immunosorbent assay (ELISA) [ Time Frame: Baseline to 12 months after completion of treatment ] [ Designated as safety issue: No ]
  • PFS [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • OS [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: February 2014
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (placebo)
Patients receive HER2 ICD peptide-based vaccine ID once monthly for 3 months, trastuzumab per standard of care, and placebo PO BID for 4 months.
Biological: HER-2/neu intracellular domain protein
Given ID
Other Names:
  • HER-2 ICD Peptide
  • HER-2/neu ICD Protein
Biological: trastuzumab
Given per standard of care
Other Names:
  • anti-c-erB-2
  • Herceptin
  • MOAB HER2
Other: placebo
Given PO
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (polysaccharide-K)
Patients receive HER2 ICD peptide-based vaccine ID and trastuzumab as in Arm I and polysaccharide-K PO BID for 4 months.
Biological: HER-2/neu intracellular domain protein
Given ID
Other Names:
  • HER-2 ICD Peptide
  • HER-2/neu ICD Protein
Biological: trastuzumab
Given per standard of care
Other Names:
  • anti-c-erB-2
  • Herceptin
  • MOAB HER2
Biological: polysaccharide-K
Given PO
Other Names:
  • Krestin
  • PSK
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the safety of polysaccharide-K (PSK) when given with a HER2 ICD peptide-based vaccine and trastuzumab.

SECONDARY OBJECTIVES:

I. To evaluate the effect of PSK on natural killer (NK) cell functional activity when given with a HER2 ICD peptide-based vaccine and trastuzumab.

TERTIARY OBJECTIVES:

I. To investigate the effect of PSK when given with a HER2 ICD peptide-based vaccine and trastuzumab 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 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 as in Arm I and polysaccharide-K PO BID for 4 months.

After completion of study treatment, patients are followed up for 8 months, and then twice annually for 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 trastuzumab monotherapy dosing per standard of care through the vaccine portion of the study
  • Patients must be at least 21 days post cytotoxic chemotherapy prior to enrollment
  • Patients must be at least 14 days post systemic steroids 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
  • Men and women of reproductive ability must agree to contraceptive use during 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 mg/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) on multi gated acquisition (MUGA) scan or echocardiogram performed 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 immunomodulators
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01922921

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Stephanie Parker    866-932-8588      
Principal Investigator: Lupe G. Salazar         
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Lupe Salazar Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT01922921     History of Changes
Other Study ID Numbers: 7866, NCI-2013-01377, 135, 7866, U19AT006028, P30CA015704
Study First Received: August 1, 2013
Last Updated: June 26, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Breast Diseases
Neoplasms
Neoplasms by Site
Krestin
Skin Diseases
Trastuzumab
Adjuvants, Immunologic
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Interferon Inducers
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Radiation-Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014