Vaccine Therapy in Treating Patients Receiving Trastuzumab For HER2-Positive Stage IIIB-IV Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT00343109
First received: June 20, 2006
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

This phase II trial is studying how well vaccine therapy works in treating patients receiving trastuzumab for HER2-positive stage IIIB- IV breast cancer. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells


Condition Intervention Phase
HER2-positive Breast Cancer
Male Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Biological: HER-2/neu intracellular domain protein
Procedure: leukapheresis
Other: laboratory biomarker analysis
Biological: sargramostim
Other: immunologic technique
Biological: synthetic tumor-associated peptide vaccine therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase II Study of a HER-2/Neu (HER2) Intracellular Domain (ICD) Peptide-Based Vaccine Administered to Patients With Locally Advanced or Stage IV HER2 Positive Breast Cancer

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Relapse-free survival [ Time Frame: At 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety as assessed by NCI CTCAE version 3.0 [ Time Frame: Baseline and 1 month following last vaccination ] [ Designated as safety issue: Yes ]
  • Immune response as assessed by HER2 specific T cell immunity and/or intramolecular epitope spreading [ Time Frame: Baseline, midpoint in the immunization schedule (prior to the 4th vaccine), 1 month after the 6th and last immunization and at 4, 8 and 12 months after the end of vaccinations ] [ Designated as safety issue: No ]
  • Correlation of RFS to the generation of an immune response [ Time Frame: Prior to the 4th vaccine, 1 month after the 6th and last immunization and at 4, 8 and 12 months after the end of vaccinations ] [ Designated as safety issue: No ]

Estimated Enrollment: 38
Study Start Date: March 2004
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive HER-2/neu intracellular domain peptide-based vaccine mixed with GM-CSF intradermally once monthly for 6 months in the absence of disease progression or unacceptable toxicity.
Biological: HER-2/neu intracellular domain protein
Given ID
Other Names:
  • HER-2 ICD Peptide
  • HER-2/neu ICD Protein
Procedure: leukapheresis
Optional correlative studies
Other: laboratory biomarker analysis
Correlative studies
Biological: sargramostim
Given ID
Other Names:
  • GM-CSF
  • Leukine
  • Prokine
Other: immunologic technique
Correlative studies
Other Names:
  • immunological laboratory methods
  • laboratory methods, immunological
Biological: synthetic tumor-associated peptide vaccine therapy
Given ID

Detailed Description:

PRIMARY OBJECTIVES:

1. To estimate the RFS in patients with HER2 positive locally advanced breast cancer vaccinated with a HER2 ICD peptide-based vaccine.

SECONDARY OBJECTIVES:

  1. To assess the safety of a HER2 ICD peptide-based vaccine administered concurrently with trastuzumab.
  2. To determine the immunogenicity of the HER2 ICD peptide based vaccine when given within one year of initiating standard treatment which includes trastuzumab.

    1. To determine the incidence of the development of T cell immunity specific for the HER2 ICD.
    2. To determine the incidence of the development of intramolecular epitope spreading.
    3. To determine the magnitude of the HER2 ICD specific CD4+ and CD8+ immune response generated with immunization.
  3. To assess whether there is an association between RFS and the development of an immune response (HER2 specific T cell immunity and/or the development of intramolecular epitope spreading).

OUTLINE:

Patients receive HER-2/neu intracellular domain peptide-based vaccine mixed with GM-CSF intradermally (ID) once monthly for 6 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1, 4, 8, and 12 months and then annually thereafter for up to 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Stage IIIB or Stage IIIC breast cancer who are within 1 year of diagnosis and initiating treatment with chemotherapy and trastuzumab; and are in complete remission
  • Stage IV breast cancer in first complete remission and defined as NED (no evidence of disease) or with stable bone only disease who are within 6 months of initiating maintenance trastuzumab
  • NED status should be documented by chest/abdominal CT, PET or PET/CT within the last 90 days
  • Bone only disease documented as stable or healed by PET, PET/CT, or MRI within the last 90 days; stable bone-only disease must be documented with bone scan performed within the last 6 months
  • HER2 overexpression by IHC of 2+ or 3+, in the primary tumor or metastasis or documented gene amplification by FISH analysis; if overexpression is 2+ by IHC, then patients must have HER2 gene amplification documented by FISH
  • Eligible subjects must have been treated to NED or stable bone only disease status with trastuzumab and/or chemotherapy and be off cytotoxic chemotherapy or immunosuppressive agents (e.g. systemic steroids) for at least 30 days prior to enrollment (concurrent hormonal therapy allowed; concurrent bisphosphonate therapy allowed)
  • Patients on trastuzumab should continue trastuzumab monotherapy per standard of care (the dosing and schedule of trastuzumab should follow standard guidelines as described below: trastuzumab 2mg/kg IV weekly or trastuzumab 6mg/kg IV every 3 weeks)
  • Subjects must have an ECOG Performance Status Score =< 1
  • Non-menopausal female subjects must agree to contraception for the remainder of their childbearing years
  • Male subjects must use an acceptable form of contraception throughout the course of the study
  • Hematocrit >= 30,000
  • Platelet count >= 100,000
  • WBC >= 3000/mcl
  • Stable creatinine =< 2.0 mg/dl or a creatinine clearance greater than 60 ml/min
  • Serum bilirubin < 1.5 mg/dl
  • SGOT < 2x ULN
  • Laboratory tests should be performed within 60 days of enrollment
  • Subjects must have recovered from major infections and/or surgical procedures and, in the opinion of the investigator, not have any significant active concurrent medical illnesses precluding protocol treatment
  • Patients on trastuzumab monotherapy must have adequate cardiac function as demonstrated by normal ejection fraction (EF) on MUGA scan or echocardiogram performed within last 6 months

Exclusion Criteria:

  • Subjects cannot be simultaneously enrolled in other treatment studies
  • Patients cannot be receiving any other concurrent immunomodulators besides trastuzumab
  • Any contraindication to receiving GM-CSF based vaccine products
  • Cardiac disease, specifically restrictive cardiomyopathy, unstable angina within the last 6 months prior to enrollment, New York Heart Association functional class III-IV heart failure on active treatment with normalized LVEF on therapy, and symptomatic pericardial effusion
  • Active autoimmune disease
  • Subjects can not have active immunodeficiency disorder, e.g. HIV
  • Cannot be pregnant or breast feeding
  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: NCT00343109

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Mary Disis Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT00343109     History of Changes
Obsolete Identifiers: NCT00369525
Other Study ID Numbers: 6166, NCI-2010-00803, BC 030289, 120
Study First Received: June 20, 2006
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on July 23, 2014