Vaccine Therapy in Treating Patients With Breast Cancer

Breast Cancer Clinical Trial

Official title:

Phase II Trial of the HER2/Neu Peptide GP2 + GM-CSF Vaccine vs GM-CSF Alone in HLA-A2+ OR the Modified HER2/Neu Peptide AE37 + GM-CSF Vaccine vs GM-CSF Alone in HLA-A2- Node-Positive and High-Risk Node-Negative Breast Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00524277
• Other study ID #: CDR0000562261
• Secondary ID: BAMC-C.2007.098W
• Status: Completed
• Phase: Phase 2
• Start date: January 2007
• Est. completion date: March 31, 2017

Study information

• Verified date: March 2020
• Source: San Antonio Military Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 456
• Est. completion date: March 31, 2017
• Est. primary completion date: December 31, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

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

6. Good performance status (as defined in Exclusion Criteria)

7. Capable of informed consent

Exclusion criteria:

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:

Inclusion criteria:

• Female or male

• Menopausal status not specified

• Immunologically intact by recall anergy testing

• Negative pregnancy test

Exclusion criteria:

• 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:

Inclusion criteria:

• See Disease Characteristics

Exclusion criteria:

• Concurrent immunosuppressive therapy including chemotherapy, steroids, or methotrexate

• Concurrent participation in another experimental treatment (except with permission of the other study investigator)

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• GP2 peptide + GM-CSF vaccine
Given intradermally every 3-4 weeks for a total of up to 6 inoculations
• GM-CSF (sargramostim)
GM-CSF given intradermally very 3-4 weeks for a total of up to 6 inoculations
• AE37 + GM-CSF vaccine
Given intradermally every 3-4 weeks for a total of up to 6 inoculations
• GM-CSF (sargramostim)
Given intradermally every 3-4 weeks for a total of up to 6 inoculations

Locations

Country	Name	City	State
Germany	Landstuhl Regional Medical Center	Landstuhl	Kirchberg
Greece	Saint Savas Cancer Hospital of Athens	Athens
United States	MedStar Good Samaritan Hospital Cancer Center	Baltimore	Maryland
United States	MedStar Union Memorial Hospital	Baltimore	Maryland
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Carl R. Darnall Army Medical Center	Fort Hood	Texas
United States	San Antonio Army Medical Center	Fort Sam Houston	Texas
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	STOH Clinical Research	San Antonio	Texas
United States	Madigan Army Medical Center - Tacoma	Tacoma	Washington
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
San Antonio Military Medical Center	Antigen Express, Inc, Norwell, Inc.

Countries where clinical trial is conducted

United States,  Germany,  Greece, 

References & Publications (2)

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. Review. — View Citation

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 B — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease recurrence	The following will be compared: disease recurrence rates between HLA-A2-negative patients receiving the AE37 + GM-CSF vaccine and HLA-A2-negative patients receiving GM-CSF alone; disease recurrence rates between HLA-A2-positive patients receiving the GP2 + GM-CSF vaccine and HLA-A2-positive patients receiving GM-CSF alone; disease recurrence rates between all four arms of the trial.	Five years (from date of enrollment to the study through the end of the follow-up period)
Secondary	Safety	Inoculations will be immediately halted if any serious adverse reactions occur which, when based upon appropriate judgment of the PI, are determined to jeopardize the patient or require medical or surgical intervention. Any death or grade 4 adverse drug experience found to be directly related to the experimental vaccine will result in suspension of patient enrollment to the study.	Local and systemic reactions to each inoculation will be monitored every six months during the regular inoculation series and the booster series.
Secondary	Immune Response	Immune response will be measured by proliferation assays, dimer assays, and ELISPOT. Delayed type hypersensitivity reactions will be compared between the vaccinated group and GM-CSF-only group.	Immune response will be measured after every monthly inoculation in the regular inoculation series and after each inoculation in the booster series

External Links

•   Clinical trial summary from the National Cancer Institute's PDQ® database