Clinical trial NCT00524277: Vaccine Therapy in Treating Patients With Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
male breast cancer
Lead sponsor: San Antonio Military Medical Center
Sponsor class: FED
Collaborators: name: NuGenerex Immuno-Oncology
name: Norwell, Inc.
First posted: 2007-09-03
Enrollment: 456
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Disease recurrence
timeFrame: Five years (from date of enrollment to the study through the end of the follow-up period)
Secondary outcomes:
measure: Safety
timeFrame: Local and systemic reactions to each inoculation will be monitored every six months during the regular inoculation series and the booster series.
measure: Immune Response
timeFrame: Immune response will be measured after every monthly inoculation in the regular inoculation series and after each inoculation in the booster series
Other outcomes:
Locations:
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Honolulu
country: United States
facility: University of Hawaii Cancer Center
state: Hawaii
city: Baltimore
country: United States
facility: MedStar Union Memorial Hospital
state: Maryland
city: Baltimore
country: United States
facility: MedStar Good Samaritan Hospital Cancer Center
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Fort Hood
country: United States
facility: Carl R. Darnall Army Medical Center
state: Texas
city: Fort Sam Houston
country: United States
facility: San Antonio Army Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: STOH Clinical Research
state: Texas
city: Tacoma
country: United States
facility: Madigan Army Medical Center - Tacoma
state: Washington
city: Landstuhl
country: Germany
facility: Landstuhl Regional Medical Center
state: Kirchberg
city: Athens
country: Greece
facility: Saint Savas Cancer Hospital of Athens
Study officials:
affiliation: UT M.D. Anderson Cancer Center
name: Elizabeth A Mittendorf, MD, FACS
role: PRINCIPAL_INVESTIGATOR
affiliation: Cancer Vaccine Development Program, Department of Surgery, Brooke Army Medical Center
name: George E Peoples, MD, FACS
role: STUDY_DIRECTOR
References:
citation: 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.
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 Biol Ther. 2011 Nov;11(11):1543-50. doi: 10.1517/14712598.2011.616889. Epub 2011 Sep 6.
citation: 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.