Vaccine Therapy in Treating Patients With Breast Cancer

NCT ID: NCT00524277

Last Updated: 2020-03-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

456 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-01-31

Study Completion Date

2017-03-31

Brief Summary

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RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells that express HER2/neu. Biological therapies, such as GM-CSF, may stimulate the immune system in different ways and stop tumor cells from growing. It is not yet known whether vaccine therapy is more effective than GM-CSF in treating breast cancer.

PURPOSE: This randomized phase II trial is studying vaccine therapy to see how well it works compared with GM-CSF in treating patients with breast cancer.

Detailed Description

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OBJECTIVES:

* To determine if the GP2 peptide/GM-CSF vaccine reduces the recurrence rate in HLA-A2-positive, HER2/neu-positive, node-positive, or high-risk node-negative breast cancer patients randomized to receive the vaccine versus the immunoadjuvant, sargramostim (GM-CSF), alone.
* To determine if the AE37 peptide/GM-CSF vaccine reduces the recurrence rate in HLA-A2-negative, HER2/neu-positive, node-positive or high-risk node-negative breast cancer patients randomized to receive the vaccine versus the immunoadjuvant, GM-CSF, alone.
* To monitor the invitro and invivo immunologic responses to the vaccines and correlate these responses with the clinical outcomes.
* To monitor for any unexpected toxicities with the vaccines.

OUTLINE: This is a multicenter study. Patients are stratified according to nodal status. Patients are randomized to 1 of 4 treatment arms.

* Arm I: HLA-A2-positive patients receive GP2 peptide/GM-CSF vaccine intradermally (ID) every 3-4 weeks for a total of up to 6 inoculations.
* Arm II: HLA-A2-positive patients receive solely GM-CSF ID
* Arm III: HLA-A2-negative patients receive AE37 peptide/GM-CSF vaccine ID every 3-4 weeks for a total of up to 6 inoculations.
* Arm IV: HLA-A2-negative patients receive solely GM-CSF ID

After completion of study therapy, patients are followed every 3 months for the first 24 months and then every 6 months for an additional 36 months.

Booster inoculations are administered at 12, 18, 24, and 30 months from the date of patients' enrollment into the study. One booster inoculation is administered at each timepoint (+/- 2 weeks) and will be the same inoculation (vaccine or GM-CSF only) as what patients received during their regular inoculation series.

Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Participants

Study Groups

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Arm I

HLA-A2-positive patients receive GP2 peptide + GM-CSF vaccine intradermally (ID) every 3-4 weeks for a total of up to 6 inoculations.

Group Type EXPERIMENTAL

GP2 peptide + GM-CSF vaccine

Intervention Type BIOLOGICAL

Given intradermally every 3-4 weeks for a total of up to 6 inoculations

Arm II

HLA-A2-positive patients receive GM-CSF ID every 3-4 weeks for a total of up to 6 inoculations.

Group Type ACTIVE_COMPARATOR

GM-CSF (sargramostim)

Intervention Type BIOLOGICAL

GM-CSF given intradermally very 3-4 weeks for a total of up to 6 inoculations

Arm III

HLA-A2-negative patients receive AE37 peptide/GM-CSF vaccine ID every 3-4 weeks for a total of up to 6 inoculations.

Group Type EXPERIMENTAL

AE37 + GM-CSF vaccine

Intervention Type BIOLOGICAL

Given intradermally every 3-4 weeks for a total of up to 6 inoculations

Arm IV

HLA-A2-negative patients receive GM-CSF ID ID every 3-4 weeks for a total of up to 6 inoculations

Group Type ACTIVE_COMPARATOR

GM-CSF (sargramostim)

Intervention Type BIOLOGICAL

Given intradermally every 3-4 weeks for a total of up to 6 inoculations

Interventions

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GP2 peptide + GM-CSF vaccine

Given intradermally every 3-4 weeks for a total of up to 6 inoculations

Intervention Type BIOLOGICAL

GM-CSF (sargramostim)

GM-CSF given intradermally very 3-4 weeks for a total of up to 6 inoculations

Intervention Type BIOLOGICAL

AE37 + GM-CSF vaccine

Given intradermally every 3-4 weeks for a total of up to 6 inoculations

Intervention Type BIOLOGICAL

GM-CSF (sargramostim)

Given intradermally every 3-4 weeks for a total of up to 6 inoculations

Intervention Type BIOLOGICAL

Other Intervention Names

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GM-CSF (sargramostim) GM-CSF (sargramostim)

Eligibility Criteria

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Inclusion Criteria

1. Lymph node-positive breast cancer or high-risk lymph node-negative breast cancer. The latter is defined by any one of the following criteria:

* T2 disease
* Grade 3 disease
* Lymphovascular invasion
* Estrogen receptor- or progesterone receptor-negative disease
* HER2/neu-expressing tumor (immunohistochemistry \[IHC\] 3+ and/or amplified fluorescence in situ hybridization \[FISH\] \>2.2, or N0 (i+))
2. HER2/neu-expressing tumor (IHC 1-3+ and or positive FISH \>1.2)
3. Completion of primary standard of care breast cancer therapies (i.e., surgery, chemotherapy, immunotherapy and radiation therapy as appropriate per standard of care for patients' specific cancer)
4. Clinically cancer-free (no evidence of disease)
5. Patients may be enrolled between 1-6 months from completion of standard primary breast cancer therapies

* Female or male
* Menopausal status not specified
* Immunologically intact by recall anergy testing
* Negative pregnancy test


* See Disease Characteristics

Exclusion Criteria

7. Capable of informed consent


1. HER2/neu-negative breast cancers (IHC 0)
2. Clinical and/or radiographic evidence of residual or persistent breast cancer
3. Receiving immunosuppressive therapy to include chemotherapy, steroids, or methotrexate
4. In poor health (Karnofsky \<60%, ECOG \>/-2)
5. Total bilirubin \>1.8, creatinine \>2, hemoglobin \<10, platelets \<50,000, WBC \<2,000)
6. Active interstitial lung disease; asthma requiring more than as needed bronchodilators for management; or other autoimmune lung disease
7. Pregnancy (urine hCG)
8. Breast feeding
9. History of autoimmune disease
10. Involved in other experimental protocols (except with permission of the other study PI)

PATIENT CHARACTERISTICS:


* Karnofsky 0-60% or ECOG ≥ 2
* Total bilirubin \> 1.8 g/dL
* Creatinine \> 2.0 g/dL
* Hemoglobin \< 10.0 g/dL
* Platelet count \< 50,000/mm³
* WBC\< 2,000/mm³
* Active pulmonary disease requiring medication that includes multiple inhalers
* Pregnancy
* Breastfeeding
* History of autoimmune disease

PRIOR CONCURRENT THERAPY:


* Concurrent immunosuppressive therapy including chemotherapy, steroids, or methotrexate
* Concurrent participation in another experimental treatment (except with permission of the other study investigator)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NuGenerex Immuno-Oncology

INDUSTRY

Sponsor Role collaborator

Norwell, Inc.

INDUSTRY

Sponsor Role collaborator

San Antonio Military Medical Center

FED

Sponsor Role lead

Responsible Party

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COL George Peoples, MD, FACS

Chief, Surgical Oncology, Brooke Army Medical Center; Director and Principal Investigator, Cancer Vaccine Development Program

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Elizabeth A Mittendorf, MD, FACS

Role: PRINCIPAL_INVESTIGATOR

UT M.D. Anderson Cancer Center

George E Peoples, MD, FACS

Role: STUDY_DIRECTOR

Cancer Vaccine Development Program, Department of Surgery, Brooke Army Medical Center

Locations

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Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

Site Status

University of Hawaii Cancer Center

Honolulu, Hawaii, United States

Site Status

MedStar Union Memorial Hospital

Baltimore, Maryland, United States

Site Status

MedStar Good Samaritan Hospital Cancer Center

Baltimore, Maryland, United States

Site Status

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Site Status

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Site Status

Carl R. Darnall Army Medical Center

Fort Hood, Texas, United States

Site Status

San Antonio Army Medical Center

Fort Sam Houston, Texas, United States

Site Status

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

STOH Clinical Research

San Antonio, Texas, United States

Site Status

Madigan Army Medical Center - Tacoma

Tacoma, Washington, United States

Site Status

Landstuhl Regional Medical Center

Landstuhl, Kirchberg, Germany

Site Status

Saint Savas Cancer Hospital of Athens

Athens, , Greece

Site Status

Countries

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United States Germany Greece

References

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Mittendorf EA, Alatrash G, Xiao H, Clifton GT, Murray JL, Peoples GE. Breast cancer vaccines: ongoing National Cancer Institute-registered clinical trials. Expert Rev Vaccines. 2011 Jun;10(6):755-74. doi: 10.1586/erv.11.59.

Reference Type BACKGROUND
PMID: 21692698 (View on PubMed)

Sears AK, Perez SA, Clifton GT, Benavides LC, Gates JD, Clive KS, Holmes JP, Shumway NM, Van Echo DC, Carmichael MG, Ponniah S, Baxevanis CN, Mittendorf EA, Papamichail M, Peoples GE. AE37: a novel T-cell-eliciting vaccine for breast cancer. Expert Opin Biol Ther. 2011 Nov;11(11):1543-50. doi: 10.1517/14712598.2011.616889. Epub 2011 Sep 6.

Reference Type RESULT
PMID: 21895539 (View on PubMed)

Jackson DO, Trappey FA, Clifton GT, Vreeland TJ, Peace KM, Hale DF, Litton JK, Murray JL, Perez SA, Papamichail M, Mittendorf EA, Peoples GE. Effects of HLA status and HER2 status on outcomes in breast cancer patients at risk for recurrence - Implications for vaccine trial design. Clin Immunol. 2018 Oct;195:28-35. doi: 10.1016/j.clim.2018.06.008. Epub 2018 Jul 17.

Reference Type DERIVED
PMID: 30025819 (View on PubMed)

Related Links

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Other Identifiers

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BAMC-C.2007.098

Identifier Type: OTHER

Identifier Source: secondary_id

WRNMMC-20225

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000562261

Identifier Type: -

Identifier Source: org_study_id

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