INCLUSION CRITERIA:
-Metastatic Breast Cancer (either male or female) with evidence of metastatic disease (must have radiographic evidence of measurable disease) on 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 NCI, or NNMC 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.
- HLA phenotype- At least 12 patients in each arm must be HLA-A2+
-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 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.
-ECOG performance status of 0 - 1.
-Serum creatinine within the institution limits of normal OR creatinine clearance on a 24 hour urine collection of greater than or equal to 60 mL/min, standard LFT limitations for patients receiving docetaxel therapy include bilirubin within ULN and SGOT/SGPT less than1.5 x ULN. If transaminases are greater than 1.5 x ULN up to 2 x ULN (as currently indicated), then alk phos should be less than 2.5 x ULN. (Patients with renal abnormalities should be evaluated for 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/mm3
2. Platelet count greater than or equal to 100,000/mm3
3. 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 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 FISH positive or IHC 3+ positive for 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 must meet on-study eligibility and exclusion criteria if they continue with vaccine therapy alone.
-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.
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 physiologic doses for systemic steroid replacement or 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.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/30/2009