Vaccine Therapy in Treating Patients With Previously Treated Stage II or Stage III Breast Cancer - Full Text View

Sponsors and Collaborators:	Mayo Clinic National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00640861

Purpose

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells.

It is not yet known which vaccine is most effective in treating breast cancer.

PURPOSE: This randomized clinical trial is studying the side effects of three different vaccine therapies and comparing the vaccines to see how well they work in treating patients with previously treated stage II or stage III breast cancer.

Condition	Intervention
Breast Cancer	Biological: CpG oligodeoxynucleotide Biological: HER-2/neu peptide vaccine Biological: MUC-1 peptide vaccine Biological: incomplete Freund's adjuvant Biological: sargramostim Other: immunoenzyme technique Other: immunologic technique

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	MUC1/HER-2/Neu Peptide Based Immunotherapeutic Vaccines for Breast Adenocarcinomas

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Sargramostim Freund's adjuvant

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Percentage of CD4+ T cells, CD8+ T cells, B cells, monocytes, and dendritic cells in a patient's peripheral blood sample as estimated by flow cytometry with a panel of monoclonal antibodies [ Designated as safety issue: No ]
Frequency of peptide-specific IFN-gamma producing T cells and peptide-specific IL-5 producing T cells estimated by ELISPOT after in vitro stimulation with peptide-sensitized stimulator cells for MUC1 and HER-2 peptides [ Designated as safety issue: No ]
Number and severity of hematologic and non-hematologic toxicities reported using the NCI-CTC version 3.0 criteria [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Disease-free survival, defined as the time from registration to the documentation of a first failure where a failure is the recurrence of breast cancer or a diagnosis of a second primary cancer [ Designated as safety issue: No ]
Overall survival, defined as the time from registration to death due to any cause [ Designated as safety issue: No ]

Estimated Enrollment:	45
Study Start Date:	August 2008
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To determine the safety and immunization efficacy of MUC1 and HER-2/neu peptide vaccines combined with CpG oligodeoxynucleotide, sargramostim (GM-CSF), or both, as immune adjuvants suspended in Freund's incomplete adjuvant in patients with previously treated stage II or III adenocarcinoma of the breast.

Secondary

To describe the impact of immunization on clinical outcomes in patients with MUC1-positive breast cancer in terms of disease-free survival and overall survival.

OUTLINE: Patients are stratified according to Her-2/neu status (positive vs negative). Patients are randomized to

1 of 3 treatment arms.

Arm A: Patients receive a vaccine comprising incomplete Freund's adjuvant, MUC1 antigen vaccine, two Her-2/neu peptide-based vaccines, and sargramostim (GM-CSF) subcutaneously (SC) on day 1.
Arm B: Patients receive a vaccine comprising incomplete Freund's adjuvant, MUC1 antigen vaccine, two Her-2/neu peptide-based vaccines (one of them different than in arm A), and CpG oligodeoxynucleotide SC on day
Arm C: Patients receive a vaccine comprising incomplete Freund's adjuvant, MUC1 antigen vaccine, two Her-2/neu peptide-based vaccines (one of them different than in arm A; the same as in arm B), GM-CSF, and CpG oligodeoxynucleotide SC on day 1. In all arms, treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients who complete 6 courses of treatment without disease recurrence or a second primary or intolerable toxicity will go to the observation phase of the study for up to 2 years. Patients who develop recurrent disease during the observational phase will go to the event monitoring phase for up to 2 years.

Blood samples are collected periodically. Blood samples and tissue samples from the patient's most recent surgery are used for correlative studies including immune responses to T helper and CTL epitopes by Elispot and tetramer analysis; and antigenic profiling by expression analysis of class I HLA antigens, MUC1, and HER-2 in tumor tissue.

After completion of study treatment, patients are followed periodically until disease recurrence or for up to 2 years.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the breast
- Clinical stage II or III disease
- No radiographic evidence of disease at the time of enrollment
- Has undergone surgery, adjuvant chemotherapy, and/or radiotherapy
  - Completed "standard first-line therapy" only (including adjuvant therapy) for breast cancer within the past 3 months and currently with no evidence of disease
- Patients with stage I breast cancer with high-risk features are eligible provided 1 of the following criteria are met:
  - HER2 over-expression or amplification
  - Triple-negative (i.e., no expression of ER, PR, or over-expression of HER2 on routine immunohistochemical staining)
.
MUC1-positive breast cancer
HLA-A2 positive
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Menopausal status not specified
ECOG performance status 0-2
Hemoglobin ≥ 8.0 g/dL
Platelet count ≥ 75,000/μL
ANC ≥ 1,500/uL
Creatinine ≤ 2 times upper limit of normal (ULN)
AST ≤ 2 times ULN
No uncontrolled infection
No known HIV infection
No other circumstances (e.g., concurrent use of systemic immunosuppressants or immunocompromising condition) that in the opinion of the physician would render the patient a poor candidate for this trial
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No prior invasive malignancies within the past 5 years (with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix)

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Fully recovered from acute, reversible effects of any prior breast cancer therapy
No more than 3 years since prior surgery for primary breast cancer
Concurrent anti-estrogen therapy is allowed
No other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-FDA-approved indication and in the context of a research investigation)
No concurrent enrollment in any other study involving a pharmacologic agent (drugs, biologics, immunotherapy approaches, gene therapy) whether for symptom control or therapeutic intent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00640861

Locations

United States, Arizona
Mayo Clinic Scottsdale	Recruiting
Scottsdale, Arizona, United States, 85259-5499
Contact: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623
United States, Minnesota
Mayo Clinic Cancer Center	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:	Svetomir Markovic, MD, PhD	Mayo Clinic
Investigator:	Sandra J. Gendler, PhD	Mayo Clinic Scottsdale

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000589446, MAYO-MC0338
Study First Received:	March 20, 2008
Last Updated:	August 4, 2009
ClinicalTrials.gov Identifier:	NCT00640861 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage I breast cancer

Study placed in the following topic categories:

Immunologic Factors
Skin Diseases
Adjuvants, Immunologic
Breast Neoplasms

Freund's Adjuvant
Adenocarcinoma
Breast Diseases
CPG-oligonucleotide

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Immunologic Factors
Skin Diseases
Physiological Effects of Drugs
Adjuvants, Immunologic

Breast Neoplasms
Freund's Adjuvant
Pharmacologic Actions
Breast Diseases
CPG-oligonucleotide

ClinicalTrials.gov processed this record on September 10, 2009