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

Primary Purpose

HER2-positive Breast Cancer, Male Breast Cancer, Recurrent Breast Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
HER-2/neu peptide vaccine
sargramostim
rintatolimod
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HER2-positive Breast Cancer focused on measuring Breast Cancer, HER2+, Vaccine, Stage II, Stage III, Stage IV

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 30 days of eligibility sign-off
  • 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

Sites / Locations

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Active Comparator

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Stage I, Arm 1 (HER-2/neu peptide vaccine and rintatolimod)

Stage II, Arm I (HER-2/neu peptide vaccine and sargramostim)

Stage II, Arm II (HER-2 vaccine, sargramostim, rintatolimod)

Stage I, Arm 2 (HER-2/neu peptide vaccine and rintatolimod)

Stage I, Arm 3 (HER-2/neu peptide vaccine and rintatolimod)

Stage I, Arm 4 (HER-2/neu peptide vaccine and rintatolimod)

Stage I; Arm 5 (HER-2/neu peptide vaccine and rintatolimod)

Arm Description

Arm 1: HER2 peptide vaccine + 4 mcg Ampligen® Five groups of randomized patients with each group receiving the synthetic HER-2/neu peptide vaccine admixed with rintatolimod (different doses).

Patients receive synthetic HER-2/neu peptide vaccine admixed with GM-CSF ID.

Patients receive synthetic HER-2/neu peptide vaccine admixed with GM-CSF and rintatolimod ID

Arm 2: HER2 peptide vaccine + 20 mcg Ampligen® Five groups of randomized patients with each group receiving the synthetic HER-2/neu peptide vaccine admixed with rintatolimod (different doses).

Arm 3: HER2 peptide vaccine + 79 mcg Ampligen® Five groups of randomized patients with each group receiving the synthetic HER-2/neu peptide vaccine admixed with rintatolimod (different doses).

Arm 4: HER2 peptide vaccine + 495 mcg Ampligen® Five groups of randomized patients with each group receiving the synthetic HER-2/neu peptide vaccine admixed with rintatolimod (different doses).

Arm 5: HER2 peptide vaccine + 2000 mcg Ampligen® Five groups of randomized patients with each group receiving the synthetic HER-2/neu peptide vaccine admixed with rintatolimod (different doses).

Outcomes

Primary Outcome Measures

Evaluation of immune response among the different treatment arms in Stage I and II
Standard interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) assay will be used to evaluate CD4+ 1 T cell responses to HER2 immunizing peptides.
Evaluation of safety and systemic toxicity among the different treatment arms in Stage I and II
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
Though not statistically powered to this endpoint, large differences if observed between the vaccine treatment groups will be noted and described.
Overall survival
Though not statistically powered to this endpoint, large differences if observed between the vaccine treatment groups will be noted and described.

Full Information

First Posted
May 16, 2011
Last Updated
February 4, 2020
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01355393
Brief Title
Vaccine Therapy in Combination With Rintatolimod and/or Sargramostim in Treating Patients With Stage II-IV HER2-Positive Breast Cancer
Official Title
Phase I-II Study of HER2 Vaccination With Poly(I) • Poly(C12U) (Ampligen®) as an Adjuvant in Optimally Treated Breast Cancer Patients
Study Type
Interventional

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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. Adjuvant therapies, such as GM-CSF and rintatolimod, are additional cancer treatments given after the primary treatment to lower the risk that the cancer will come back and are one way to help vaccines produce stronger immune responses. Giving vaccine therapy together with rintatolimod and/or GM-CSF may be a safe and effective treatment for breast cancer.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
Breast Cancer, HER2+, Vaccine, Stage II, Stage III, Stage IV

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Stage I, Arm 1 (HER-2/neu peptide vaccine and rintatolimod)
Arm Type
Experimental
Arm Description
Arm 1: HER2 peptide vaccine + 4 mcg Ampligen® Five groups of randomized patients with each group receiving the synthetic HER-2/neu peptide vaccine admixed with rintatolimod (different doses).
Arm Title
Stage II, Arm I (HER-2/neu peptide vaccine and sargramostim)
Arm Type
Active Comparator
Arm Description
Patients receive synthetic HER-2/neu peptide vaccine admixed with GM-CSF ID.
Arm Title
Stage II, Arm II (HER-2 vaccine, sargramostim, rintatolimod)
Arm Type
Experimental
Arm Description
Patients receive synthetic HER-2/neu peptide vaccine admixed with GM-CSF and rintatolimod ID
Arm Title
Stage I, Arm 2 (HER-2/neu peptide vaccine and rintatolimod)
Arm Type
Experimental
Arm Description
Arm 2: HER2 peptide vaccine + 20 mcg Ampligen® Five groups of randomized patients with each group receiving the synthetic HER-2/neu peptide vaccine admixed with rintatolimod (different doses).
Arm Title
Stage I, Arm 3 (HER-2/neu peptide vaccine and rintatolimod)
Arm Type
Experimental
Arm Description
Arm 3: HER2 peptide vaccine + 79 mcg Ampligen® Five groups of randomized patients with each group receiving the synthetic HER-2/neu peptide vaccine admixed with rintatolimod (different doses).
Arm Title
Stage I, Arm 4 (HER-2/neu peptide vaccine and rintatolimod)
Arm Type
Experimental
Arm Description
Arm 4: HER2 peptide vaccine + 495 mcg Ampligen® Five groups of randomized patients with each group receiving the synthetic HER-2/neu peptide vaccine admixed with rintatolimod (different doses).
Arm Title
Stage I; Arm 5 (HER-2/neu peptide vaccine and rintatolimod)
Arm Type
Experimental
Arm Description
Arm 5: HER2 peptide vaccine + 2000 mcg Ampligen® Five groups of randomized patients with each group receiving the synthetic HER-2/neu peptide vaccine admixed with rintatolimod (different doses).
Intervention Type
Biological
Intervention Name(s)
HER-2/neu peptide vaccine
Other Intervention Name(s)
HER-2
Intervention Description
Given ID
Intervention Type
Biological
Intervention Name(s)
sargramostim
Other Intervention Name(s)
GM-CSF, Leukine, Prokine
Intervention Description
Given ID
Intervention Type
Drug
Intervention Name(s)
rintatolimod
Other Intervention Name(s)
Ampligen, atvogen, poly(I):poly(C12U) RNA
Intervention Description
Given ID
Primary Outcome Measure Information:
Title
Evaluation of immune response among the different treatment arms in Stage I and II
Description
Standard interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) assay will be used to evaluate CD4+ 1 T cell responses to HER2 immunizing peptides.
Time Frame
Up to 12 months post-vaccination
Title
Evaluation of safety and systemic toxicity among the different treatment arms in Stage I and II
Description
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.
Time Frame
Up to 4 months
Secondary Outcome Measure Information:
Title
Disease-free survival
Description
Though not statistically powered to this endpoint, large differences if observed between the vaccine treatment groups will be noted and described.
Time Frame
Time from study enrollment to time of first event, assessed up to 12 months post-vaccination
Title
Overall survival
Description
Though not statistically powered to this endpoint, large differences if observed between the vaccine treatment groups will be noted and described.
Time Frame
Time from study enrollment to time of first event, assessed up to 12 months post-vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 30 days of eligibility sign-off 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lupe Salazar
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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