A Randomized Pilot Phase II Study of Docetaxel Alone or in Combination With PANVAC(Trademark)-V (Vaccinia) and PANVAC(Trademark)-F (Fowlpox) in Adults With Metastatic Breast Cancer

Inclusion Criteria

- INCLUSION CRITERIA:

- Metastatic Breast Cancer (either male or female) with evidence of metastatic disease
(must have radiographic evidence of measurable disease) on computed tomography (CT)
scan or X-ray, or evidence of evaluable disease on bone scan that is consistent with
metastasis and a life expectancy of at least 4 months. Patients may have received
unlimited prior hormonal therapy and chemotherapy.

- Histologically confirmed adenocarcinoma of the breast cancer confirmed in the
Pathology Clinical Center at National Cancer Institute (NCI), (or National Naval
Medical Center (NNMC)) or MD Anderson Pathology Department prior to starting this
study. Note: However, if no pathologic specimen is available, patients may enroll
with a clinical course consistent with breast cancer and a pathological documentation
of the disease.

- 18 years of age or greater.

- May have received docetaxel in the adjuvant setting at least 12 months prior to study
entry.

- Able to understand and give informed consent.

- Able to avoid close household contact (close household contacts are those who share
housing or have close physical contact) for at least two weeks after recombinant
vaccinia vaccination with persons with active or a history of eczema or other
eczematoid skin disorders; those with other acute, chronic or exfoliative skin
conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne,
or other open rashes or wounds) until condition resolves; pregnant or nursing women;
children 3 years of age and under; and immunodeficient or immunosuppressed persons
(by disease or therapy), including human immunodeficiency virus (HIV) infection. We
have vaccinated over 700 cancer patients and have reported no cases of either self
inoculation or person to person transmission of the virus.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.

- Serum creatinine less than 1.5 times upper limits of normal (ULN) OR creatinine
clearance on a 24 hour urine collection of greater than or equal to 60 mL/min,
standard liver function tests (LFT) limitations for patients receiving docetaxel
therapy include bilirubin within ULN and serum glutamic oxaloacetic transaminase
(SGOT)/serum glutamic pyruvic transaminase (SGPT) less than 1.5 times the ULN. If
transaminases are greater than 1.5 times the ULN up to 2 times the ULN (as currently
indicated), then alk phos should be less than 2.5 times the ULN. (Patients with
renal abnormalities should be evaluated for creatinine clearance (CrCl) and
interstitial abnormalities. A Cr Cl of greater than or equal to 60ml/min measured or
calculated and proteinuria less than 1000mg per 24 hours are eligible unless
explained by non-renal causes.)

- Recovered completely from any grade 3 or 4 reversible hematologic and non hematologic
toxicity associated with recent therapy. Typically this is 3-4 weeks for patients who
most recently received cytotoxic therapy. Patients previously treated with mitomycin
c or carboplatin will require a minimum of 6 weeks.

- Hematological eligibility parameters (within 16 days of starting therapy):

1. Granulocyte count greater than or equal to1,500/mm^3

2. Platelet count greater than or equal to 100,000/mm^3

3. Hemoglobin (Hgb) greater than or equal to 8 Gm/dL

- Must agree to use effective birth control or abstinence during and for a period of 4
months after the last vaccination therapy.

- Patients whose tumors are estrogen receptor (ER) positive should have failed primary
hormone therapy unless clinically indicated, i.e. in patients with visceral disease
or symptomatic bone disease where up front chemotherapy is warranted. Patients who
progressed or recurred following Trastuzumab (Herceptin) therapy if a patient is
fluorescence in situ hybridization (FISH) positive or immunohistochemistry (IHC) 3+
positive for human epidermal growth factor receptor 2 (Her-2 neu). Those patients who
have progressed on trastuzumab may continue to receive the drug by their referring
physician. However, if trastuzumab has been discontinued at the time of enrolling on
study, it cannot be resumed while a patient remains on study.

- Patients randomized to docetaxel alone (arm B) may at time of progression go on to
receive vaccine alone if their ECOG performance status remains 0-1, and they do not
have any uncontrolled pain or organ dysfunction that would require another
intervention such as radiation or chemotherapy.

Furthermore, patients initially randomized to arm B that would like to cross over and
continue vaccine therapy must meet on-study eligibility and exclusion criteria with the
exception of liver transaminase requirement. Patients with liver transaminase levels
within Grade 1 by Common Terminology Criteria for Adverse Events (CTCAE) v4.0 (up to 3 x
ULN) will be allowed to crossover to vaccine.

- Patients should appear clinically stable (in the opinion of the principle
investigator) to complete the full 3 month course of vaccination with an anticipated
survival of 6 months or longer.

- No other active malignancies within the past 12 months (with the exception of
non-melanoma skin cancers or carcinoma in situ of the bladder) or life threatening
illnesses.

- Patients with cardiovascular symptoms should be fully evaluated for signs and
symptoms of cardiovascular disease and other standard evaluations including
electrocardiogram (EKG), chest X-ray, cardiac enzymes, and echocardiogram as
clinically indicated.

EXCLUSION CRITERIA:

- Patients should have no evidence of being immunocompromised as listed below.

1. Human immunodeficiency virus positivity due to the potential for decreased
tolerance and risk for severe side effects

2. Active autoimmune diseases requiring treatment or a history of autoimmune
disease that might be stimulated by vaccine treatment. This requirement is due
to the potential risks of exacerbating autoimmunity Patients with endocrine
disease that is controlled by replacement therapy including thyroid disease and
adrenal disease and vitiligo may be enrolled

3. Concurrent use of systemic steroids, except for local (topical, nasal, or
inhaled) steroid use

- History of allergy or untoward reaction to prior vaccination with vaccinia virus.

- Pregnant or breast-feeding women

- Altered immune function, including immunodeficiency or history of immunodeficiency;
eczema; history of eczema, or other eczematoid skin disorders; or those with acute,
chronic or exfoliative skin conditions (e.g. atopic dermatitis, burns, impetigo,
varicella zoster, severe acne, or other open rashes or wounds)

- Serious intercurrent medical illness which would interfere with the ability of the
patient to carry out the treatment program, including, but not limited to,
inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active
diverticulitis

- Clinically active brain metastasis, or a history of seizures that have been active
within one year

- Medical conditions, which, in the opinion of the investigators would jeopardize the
patient or the integrity of the data obtained

- Prior docetaxel chemotherapy for metastatic disease

- Serious hypersensitivity reaction to egg products

- Clinically significant cardiomyopathy requiring treatment

- Chronic hepatitis infection, including B and C, because of potential immune
impairment

- Although topical steroids are allowed, steroid eye-drops are contraindicated

- Patients who have received prior PANVAC vaccine therapy

- Patients with a prior history of allergy to eggs or egg products should not receive
the vaccine

- Patients with cardiac disease that have fatigue, palpitation, dyspnea or angina with
ordinary physical activity (New York Heart Association class 2 or greater) are not
eligible.

- Prior splenectomy.

- Cardiac complications, including recent myocardial infarction or cerebrovascular
accident within one year, and/or unstable or uncontrolled angina.