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A Safety and Bioactivity Study of Combination Therapy With Trastuzumab, Cyclophosphamide, and an Allogeneic GM-CSF-Secreting Breast Tumor Vaccine for the Treatment of Patients With High Risk/ Metastatic HER-2/Neu- Overexpressing Breast Cancer With No Evidence of Disease


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Breast Cancer

Thank you

Trial Information

A Safety and Bioactivity Study of Combination Therapy With Trastuzumab, Cyclophosphamide, and an Allogeneic GM-CSF-Secreting Breast Tumor Vaccine for the Treatment of Patients With High Risk/ Metastatic HER-2/Neu- Overexpressing Breast Cancer With No Evidence of Disease


OBJECTIVES:

Primary

- To evaluate the safety of allogeneic sargramostim (GM-CSF)-secreting breast cancer
vaccine in combination with trastuzumab (Herceptin®) and cyclophosphamide in patients
with high-risk or metastatic HER2/neu-overexpressing breast cancer.

- To measure the HER2/neu-specific CD4+ T-cell response by delayed-type hypersensitivity.

- To measure the magnitude of HER2/neu-specific CD8+ T-cell responses by ELISPOT.

Secondary

- To assess the impact of trastuzumab on immune priming in vivo by IHC.

- To measure the impact of cyclophosphamide pretreatment on CD4+CD25+ regulatory T cells
by flow cytometry.

- To determine the time to disease progression.

Tertiary

- To develop the tandem tetramer/CD107a cytotoxicity assay for HER2/neu-specific CD8+ T
cells.

- To measure novel T-cell responses induced by trastuzumab and cyclophosphamide-modulated
vaccination.

OUTLINE: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes once weekly
beginning on day -1 of the first course of vaccination and continuing until the completion
of the last course of vaccination. Patients also receive cyclophosphamide IV over 30 minutes
on day -1 and allogeneic sargramostim (GM-CSF)-secreting breast cancer vaccine intradermally
on day 0. Treatment with cyclophosphamide and the vaccine repeats every 27-42 days for up to
3 courses in the absence of disease progression or unacceptable toxicity. Patients then
receive a fourth course of cyclophosphamide and vaccine approximately 6-8 months after the
first course.

Patients undergo delayed-type hypersensitivity testing and blood sample collection at
baseline and periodically during study for immunologic laboratory studies. Blood samples are
analyzed for serum GM-CSF levels by pharmacokinetic studies and for immune monitoring by
ELISPOT and flow cytometry. Skin punch biopsies are also performed periodically and analyzed
by IHC.

After completion of study treatment, patients are followed periodically.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the breast, meeting one of the following
criteria:

- Metastatic disease

- High-risk disease, defined as early-stage disease with pathologic involvement of
locoregional lymph nodes

- Patients who are/will be receiving standard adjuvant trastuzumab
[Herceptin®] for high-risk disease will participate in this study during
the single-agent trastuzumab portion of their therapy

- No clinical or radiographical evidence of active disease

- Not eligible for therapy of known curative potential for metastatic breast cancer

- HER2/neu-overexpressing disease, defined as HER2/neu positive by IHC 3+ staining or
by FISH+ amplification

- Stable CNS disease allowed provided it has been adequately treated and is not under
active treatment

- Hormone receptor status not specified

PATIENT CHARACTERISTICS:

- Menopausal status not specified

- ECOG performance status 0-1

- ANC > 1,000/mm^3

- Platelet count > 100,000/mm^3

- Serum creatinine < 2.0 mg/dL

- Serum bilirubin ≤ 2.0 mg/dL (unless elevation is due to known Gilbert's syndrome)

- AST/ALT ≤ 2 times upper limit of normal (ULN)

- Alkaline phosphatase ≤ 5 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Cardiac ejection fraction normal by MUGA OR ≥ 45% by ECHO

- No other malignancies within the past 5 years, except for carcinoma in situ of the
cervix, superficial nonmelanoma skin cancer, or superficial bladder cancer

- No prior or currently active autoimmune disease* requiring management with systemic
immunosuppression, including any of the following:

- Inflammatory bowel disease

- Systemic vasculitis

- Scleroderma

- Psoriasis

- Multiple sclerosis

- Hemolytic anemia or immune-mediated thrombocytopenia

- Rheumatoid arthritis

- Systemic lupus erythematosus

- Sjögren syndrome

- Sarcoidosis

- Other rheumatologic disease

- No symptomatic intrinsic lung disease or extensive tumor involvement of the lungs
resulting in dyspnea at rest

- HIV-negative

- No evidence of active acute or chronic infection

- No uncontrolled medical problems

- No active major medical or psychosocial problems that could be complicated by study
participation

- No corn allergy

- No known severe hypersensitivity to trastuzumab (except for mild to moderate infusion
reactions that are easily managed and do not recur) NOTE: *Asthma or chronic
obstructive pulmonary disease that does not require daily systemic corticosteroids
allowed

PRIOR CONCURRENT THERAPY:

- Any number of prior chemotherapy regimens for metastatic breast cancer allowed

- Prior or concurrent trastuzumab in the adjuvant or metastatic setting allowed

- More than 28 days since prior and no concurrent systemic oral steroids

- Topical, ocular, or nasal steroids allowed

- More than 28 days since prior and no concurrent chemotherapy, radiotherapy, or
biologic therapy (except trastuzumab)

- More than 28 days since prior and no concurrent participation in another
investigational clinical trial involving a new drug

- Concurrent endocrine therapy or bisphosphonates allowed

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety (local and systemic toxicity) as assessed by NCI CTCAE v3.0

Outcome Time Frame:

4 years

Safety Issue:

Yes

Principal Investigator

Leisha A. Emens, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

J0885 CDR0000634155

NCT ID:

NCT00847171

Start Date:

December 2008

Completion Date:

June 2013

Related Keywords:

  • Breast Cancer
  • male breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • stage IV breast cancer
  • HER2-positive breast cancer
  • Breast Neoplasms

Name

Location

Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410