Vaccine Therapy in Combination With Rintatolimod and/or Sargramostim in Patients With Stage II-IV HER2-Positive Breast Cancer

This study is currently recruiting participants.
Verified November 2013 by University of Washington
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT01355393
First received: May 16, 2011
Last updated: November 18, 2013
Last verified: November 2013
  Purpose

This randomized phase I/II trial studies the side effects and best dose of rintatolimod when given together with vaccine therapy and sargramostim (GM-CSF) to see how well it works in treating patients with stage II-IV human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Vaccines made from synthetic HER2/neu peptides may help the body build an effective immune response to kill tumor cells that express HER-2/neu. Our group has developed vaccines against the HER2 protein that create immune responses and in this study we are researching different ways that we may be able to make that immune response even better. Adjuvants are one way to help vaccines produce stronger immune responses. Our group has typically used the adjuvant GM-CSF and in this study we would like to look at another adjuvant called rintatolimod. Giving vaccine therapy together with rintatolimod and/or GM-CSF may be an effective treatment for breast cancer.


Condition Intervention Phase
HER2-positive Breast Cancer
Male Breast Cancer
Recurrent Breast Cancer
Stage II Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Biological: HER-2/neu peptide vaccine
Biological: sargramostim
Drug: rintatolimod
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I-II Study of HER2 Vaccination With Poly(I) • Poly(C12U) (Ampligen®) as an Adjuvant in Optimally Treated Breast Cancer Patients

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Evaluation of immune response among the different treatment arms in Stage I and II [ Time Frame: Up to 12 months post-vaccination ] [ Designated as safety issue: No ]
    Use standard interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) assay to evaluate CD4+ Th1 T cell responses to HER2 immunizing peptides.

  • Evaluation of safety and systemic toxicity among the different treatment arms in Stage I and II [ Time Frame: Up to 4 months ] [ Designated as safety issue: Yes ]
    Toxicity grading will be evaluated per Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) 4.0 and monitoring of adverse events (AEs) will be done per Food and Drug Administration (FDA) and National Cancer Institute (NCI) guidelines.


Secondary Outcome Measures:
  • Disease-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Though not statistically powered to this endpoint, large differences if observed between the vaccine treatment groups will be noted and described.

  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Though not statistically powered to this endpoint, large differences if observed between the vaccine treatment groups will be noted and described.


Estimated Enrollment: 98
Study Start Date: July 2011
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stage I (HER-2/neu peptide vaccine and rintatolimod)
Five groups of randomized patients with each group receiving the synthetic HER-2/neu peptide vaccine admixed with rintatolimod (different doses).
Biological: HER-2/neu peptide vaccine
Synthetic HER-2/neu peptide vaccine given ID
Other Name: HER-2
Drug: rintatolimod
Given ID
Other Names:
  • Ampligen
  • atvogen
  • poly(I):poly(C12U) RNA
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Stage II, Arm I (HER-2/neu peptide vaccine and sargramostim)
Patients receive synthetic HER-2/neu peptide vaccine admixed with GM-CSF ID.
Biological: HER-2/neu peptide vaccine
Synthetic HER-2/neu peptide vaccine given ID
Other Name: HER-2
Biological: sargramostim
GM-CSF given ID
Other Names:
  • GM-CSF
  • Leukine
  • Prokine
Other: laboratory biomarker analysis
Correlative studies
Experimental: Stage II, Arm II (HER-2 vaccine, sargramostim, rintatolimod)
Patients receive synthetic HER-2/neu peptide vaccine admixed with GM-CSF and rintatolimod ID
Biological: HER-2/neu peptide vaccine
Synthetic HER-2/neu peptide vaccine given ID
Other Name: HER-2
Biological: sargramostim
GM-CSF given ID
Other Names:
  • GM-CSF
  • Leukine
  • Prokine
Drug: rintatolimod
Given ID
Other Names:
  • Ampligen
  • atvogen
  • poly(I):poly(C12U) RNA
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

OBJECTIVES:

I. To choose the most promising (maximum biologic dose [MBD]) of five different doses (4, 20, 79, 495 and 2000 mcg) of Ampligen (rintatolimod) administered intradermally (i.d.) as an adjuvant with HER2 vaccination, with respect to toxicity and incidence and magnitude of immune response.

II. To determine, using MBD of Ampligen (defined in first primary aim), whether Ampligen when given with GM-CSF as a combined adjuvant strategy with HER2 vaccination increases both the incidence and magnitude of HER2 Th1 immunity as compared to the standard GM-CSF adjuvant strategy.

OUTLINE: This will be a phase I-II randomized two-stage HER2 vaccine study in breast cancer patients.

STUDY STAGE I: There are five groups of patients randomized to 1 of 5 arms with each arm receiving the synthetic HER-2/neu peptide vaccine admixed with rintatolimod (different doses) given i.d.

STUDY STAGE II: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive the synthetic HER-2/neu peptide vaccine admixed with rintatolimod given i.d.

ARM II: 24 patients will receive the HER-2/neu peptide vaccine admixed with GM-CSF and the other 24 patients will receive the HER-2/neu peptide vaccine admixed with GM-CSF in addition to rintatolimod (dose set by Stage I group that had the most active response) given i.d.

In both study stages, treatment repeats every month for up to 3 months in the absence of disease progression or unacceptable toxicity.

After completion of last vaccine, patients are followed up at 1 and 12 months.

  Eligibility

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

Inclusion Criteria:

  • Patients with stage II, or III HER2+ breast cancer who have completed definitive standard treatment and are in complete remission - or -
  • Patients with stage IV HER2+ breast cancer treated to:

    • No evidence of disease, or
    • Stable bone only disease after definitive therapy
  • Patients must have demonstrated HER2 positive disease, by one of the following methods:

    • Immunohistochemical (IHC) staining of 1+, 2+ or 3+ for the HER2 protein, or
    • Amplification of the HER2 gene on fluorescence in situ hybridization (FISH)
  • Patients must be at least 14 days post cytotoxic chemotherapy prior to enrollment
  • Patients must be at least 14 days post systemic steroids prior to enrollment
  • Patients on bisphosphonates or continued hormone therapy are eligible
  • Men and women of reproductive ability 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 any significant active concurrent medical illnesses precluding protocol treatment
  • White blood cell count (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 on trastuzumab monotherapy must have adequate cardiac function as demonstrated by normal ejection fractions (EF) on multi gated acquisition scan (MUGA) scan or echocardiogram performed within the last 3 months of eligibility sign off

Exclusion Criteria:

  • 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 rhuGM-CSF based products
  • Patients with any clinically significant autoimmune disease requiring active treatment
  • Patients receiving any concurrent immunomodulators within the last 30 days
  • Patients who are pregnant or breast-feeding
  • Patients who are simultaneously enrolled in any other treatment study
  • Patients who have received a previous HER2 breast cancer vaccine
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01355393

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Stephanie Parker    206-543-6620    TVGTrial@uw.edu   
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: NCT01355393     History of Changes
Other Study ID Numbers: 7425, NCI-2011-00658, 133 [Tumor Vaccine Group], P30CA015704
Study First Received: May 16, 2011
Last Updated: November 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Washington:
Breast Cancer
HER2+
Vaccine
Stage II
Stage III
Stage IV

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Ampligen
Poly I-C
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Interferon Inducers
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 16, 2014