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A Phase I Vaccine Safety and Chemotherapy Dose-Finding Trial of an Allogeneic GM-CSF-Secreting Breast Cancer Vaccine Given in a Specifically Timed Sequence With Immunomodulatory Doses of Cyclophosphamide and Doxorubicin


Phase 1
18 Years
N/A
Not Enrolling
Female
Breast Cancer

Thank you

Trial Information

A Phase I Vaccine Safety and Chemotherapy Dose-Finding Trial of an Allogeneic GM-CSF-Secreting Breast Cancer Vaccine Given in a Specifically Timed Sequence With Immunomodulatory Doses of Cyclophosphamide and Doxorubicin


OBJECTIVES:

Primary

- Determine the safety of vaccination comprising allogeneic sargramostim
(GM-CSF)-secreting breast cancer cells with or without immunomodulation using
cyclophosphamide and doxorubicin in women with stage IV breast cancer.

- Determine the doses of cyclophosphamide and doxorubicin that maximize vaccine-induced
immunity, in terms of immune response to HER2/neu, in patients treated with these
regimens.

- Compare in vivo immune response induced by these regimens, as measured by
immunohistochemical analysis of vaccine site biopsies from these patients, with
responses seen in prior preclinical and clinical studies.

Secondary

- Determine the time to disease progression in patients treated with these regimens.

OUTLINE: This is a dose-finding study.

The first 6 patients receive 1 of 2 doses of vaccine comprising allogeneic sargramostim
(GM-CSF)-secreting breast cancer cells intradermally (ID) on day 0. Subsequent patients
receive cyclophosphamide IV on day -1, vaccine at the higher dose ID on day 0, and
doxorubicin IV on day 7. Treatment in all patients repeats every 4-6 weeks for 3 courses in
the absence of disease progression or unacceptable toxicity. Patients with stable or
responding disease after the third course receive a fourth course of treatment at
approximately 4 months after completion of the third course.

Cohorts of 2-3 patients receive a fixed dose of vaccine in combination with escalating doses
of doxorubicin and cyclophosphamide. Doses of cyclophosphamide and doxorubicin are escalated
until an optimal dose of combination chemotherapy with a fixed dose of vaccine is achieved.

Patients are followed at 1 month and 4 months after completion of study therapy and then
annually thereafter.

PROJECTED ACCRUAL: A total of 6-60 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the breast

- Stage IV disease

- Stable disease for ≥ 28 days

- Measurable or evaluable disease OR no evidence of disease

- Not eligible for potentially curative therapy

- Adequately treated CNS metastases are allowed

- Hormone receptor status:

- Not specified

- HER-2/neu status:

- Not specified

PATIENT CHARACTERISTICS:

Age

- 18 and over

Sex

- Female

Menopausal status

- Not specified

Performance status

- ECOG 0-1

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count > 1,000/mm^3

- Platelet count > 100,000/mm^3

Hepatic

- Bilirubin ≤ 2.0 mg/dL (unless due to Gilbert's syndrome)

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

- Alkaline phosphatase ≤ 5 times ULN

Renal

- Creatinine < 2.0 mg/dL

Cardiovascular

- Ejection fraction ≥ 45% by echocardiogram or MUGA

Pulmonary

- Asthma or chronic obstructive pulmonary disease allowed provided daily systemic
corticosteroid therapy is not required

Immunologic

- No active autoimmune disease requiring systemic immunosuppressive therapy, including
any of the following:

- Inflammatory bowel disease

- Systemic vasculitis

- Scleroderma

- Psoriasis

- Multiple sclerosis

- Hemolytic anemia

- Immune-mediated thrombocytopenia

- Rheumatoid arthritis

- Systemic lupus erythematosus

- Sjögren's syndrome

- Sarcoidosis

- Other rheumatologic disease

- HIV negative

- No active acute or chronic infection

- No allergy to corn

Other

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

- No active major medical or psychosocial problem that would preclude study
participation

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after study
participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

- More than 28 days since prior biologic therapy

- No other concurrent biologic therapy, including trastuzumab (Herceptin®)

Chemotherapy

- Prior adjuvant chemotherapy allowed

- Prior doxorubicin and cyclophosphamide allowed

- Prior doxorubicin dose combined with planned study therapy dose must not exceed
a lifetime cumulative dose of ≥ 450 mg/m^2

- More than 28 days since prior systemic chemotherapy

- No other concurrent systemic chemotherapy

Endocrine therapy

- More than 28 days since prior systemic corticosteroids

- Concurrent hormonal or endocrine therapy allowed

- No concurrent systemic corticosteroids

Radiotherapy

- More than 28 days since prior radiotherapy

- No concurrent radiotherapy

Surgery

- Not specified

Other

- More than 28 days since prior participation in another investigational drug trial

- No other concurrent investigational drugs

- Concurrent bisphosphonates allowed

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Toxicity of vaccine w/ & w/o cyclophosphamide+doxorubicin by history and phys. exam. at 28-42 days after each vaccination, 56-84 days after third vaccination, 6 months after first vaccination, and annually after first vaccination

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:

J0085 CDR0000391826

NCT ID:

NCT00093834

Start Date:

January 2004

Completion Date:

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • Breast Neoplasms

Name

Location

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