A Randomized, Open-Label Comparative Study of Combination Therapy With Cyclophosphamide and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine With or Without Trastuzumab for the Treatment of Metastatic Breast Cancer That Does NOT Over-express HER-2/Neu
18 Years
N/A
Both
Breast Cancer
Trial Information
A Randomized, Open-Label Comparative Study of Combination Therapy With Cyclophosphamide and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine With or Without Trastuzumab for the Treatment of Metastatic Breast Cancer That Does NOT Over-express HER-2/Neu
OBJECTIVES:
Primary
- To evaluate the safety of cyclophosphamide-modulated vaccination with vs without
trastuzumab in patients with breast cancer that does not overexpress HER-2/neu.
- To compare the clinical benefit of cyclophosphamide-modulated vaccination with vs
without trastuzumab in these patients.
- To measure HER-2/neu-specific CD4+ and CD8+ T-cell immunity by delayed-type
hypersensitivity (DTH) and ELISPOT.
- To measure the pharmacodynamics of CD4+CD25+ regulatory T cells by flow cytometry.
Secondary
- To assess the impact of trastuzumab on immune priming in vivo by immunohistochemistry
of vaccine-site biopsies at day +3 and day +7 of courses 1 and 3 on the two study arms,
comparing cellular infiltrates to those seen in previous preclinical and clinical
models.
- To measure hTERT-specific CD8+ T-cell immunity by ELISPOT.
- To characterize the peripheral-memory T-cell pool.
Tertiary
- To determine baseline and change in vaccine site-draining lymph node immunohistology
and gene expression profile.
- To develop the tandem tetramer/CD107a cytotoxicity assay for HER-2/neu-specific CD8+ T
cells.
- To measure novel T-cell responses induced by trastuzumab and cyclophosphamide-modulated
vaccination.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic
GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6
weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Patients then receive a fourth vaccination at 6-8 months.
- Arm II: Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab
IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the
absence of disease progression or unacceptable toxicity. Patients then receive a fourth
vaccination at 6-8 months.
Skin punch and lymph node biopsies are collected at baseline and on days +3 and +7 of
courses 1 and 3 for biomarker analysis.
After completion of study treatment, patients are followed periodically.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma of the breast
- Does not overexpress HER-2/neu, defined as FISH negative or 0, 1+, or 2+ by IHC
- Stage IV disease
- Must not be eligible for therapy of known curative potential for metastatic breast
cancer
- Measurable or evaluable disease
- Stable CNS disease allowed provided that it's adequately treated and 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
- Platelets > 100,000/mm^3
- Serum bilirubin < 2.0 mg/dL (unless due to Gilbert syndrome)
- AST and ALT < 2 times upper limit of normal (ULN)
- Alkaline phosphatase < 5 times ULN
- Serum creatinine < 2.0 mg/dL
- Ejection fraction normal by MUGA OR ≥ 50% by echocardiogram
- Not pregnant or nursing
- Fertile patients must use effective contraception
- HIV negative
- Asthma or chronic obstructive pulmonary disease that does not require daily systemic
corticosteroids allowed
- No prior or concurrent 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
- Sjogren syndrome
- Sarcoidosis
- Other rheumatologic disease
- No other malignancies within the past 5 years, except carcinoma in situ of the
cervix, superficial nonmelanoma skin cancer, superficial bladder cancer, or
tamoxifen-related endometrial cancer that has been adequately treated
- No active major medical or psychosocial problems that could be complicated by study
participation
- No symptomatic intrinsic lung disease or extensive tumor involvement of the lungs
resulting in dyspnea at rest
- No uncontrolled medical problems
- No evidence of active acute or chronic infection
- No known severe hypersensitivity to trastuzumab, except mild to moderate infusion
reactions that are easily managed and do not recur
- No allergy to corn
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- More than 28 days since prior and no other concurrent chemotherapy, radiation
therapy, or biologic therapy (except trastuzumab)
- Concurrent endocrine therapy and supportive therapy with bisphosphonates allowed
- More than 28 days since prior and no other concurrent participation in an
investigational new drug trial
- More than 28 days since prior and no other concurrent systemic oral steroids
- Topical, ocular, and nasal steroids allowed
- No prior vaccination with the allogeneic GM-CSF-secreting breast tumor vaccine
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Toxicity as assessed by NCI CTCAE v3.0
Outcome Time Frame:
3 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:
J0947 CDR0000653173
NCT ID:
NCT00971737
Start Date:
July 2009
Completion Date:
Related Keywords:
- Breast Cancer
- stage IV breast cancer
- male breast cancer
- Breast Neoplasms
Name | Location |
|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
