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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


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

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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 HopkinsBaltimore, Maryland  21231-2410